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Erschienen in: Immunologic Research 2-3/2011

01.08.2011 | UNIVERSITY OF PITTSBURGH IMMUNOLOGY 2011

Phosphatidylinositol-3-kinase activity during in vitro dendritic cell generation determines suppressive or stimulatory capacity

verfasst von: Valentina Di Caro, Antonella D’Anneo, Brett Phillips, Carl Engman, Jo Harnaha, Massimo Trucco, Nick Giannoukakis

Erschienen in: Immunologic Research | Ausgabe 2-3/2011

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Abstract

Modulating PI3K at different stages of dendritic cells (DC) generation could be a novel means to balance the generation of immunosuppressive versus immunostimulatory DC. We show that PI3K inhibition during mouse DC generation in vitro results in cells that are potently immunosuppressive and characteristic of CD8alpha− CD11c+ CD11b+ DC. These DC exhibited low surface class I and class II MHC, CD40, and CD86 and did not produce TNF-alpha. In allogeneic MLR, these DC were suppressive. Although in these mixed cultures, there was no increase in the frequency of CD4+ CD25+ Foxp3+ cells, the Foxp3 content on a per cell basis was significantly increased. Sustained TLR9 signaling in the presence of PI3K inhibition during DC generation overrode the cells’ suppressive phenotype.
Literatur
1.
Zurück zum Zitat Fruman DA, Bismuth G. Fine tuning the immune response with PI3K. Immunol Rev. 2009;228(1):253–72.PubMedCrossRef Fruman DA, Bismuth G. Fine tuning the immune response with PI3K. Immunol Rev. 2009;228(1):253–72.PubMedCrossRef
2.
Zurück zum Zitat Ghigo A, Damilano F, Braccini L, Hirsch E. PI3K inhibition in inflammation: toward tailored therapies for specific diseases. Bioessays. 2010;32(3):185–96.PubMedCrossRef Ghigo A, Damilano F, Braccini L, Hirsch E. PI3K inhibition in inflammation: toward tailored therapies for specific diseases. Bioessays. 2010;32(3):185–96.PubMedCrossRef
4.
Zurück zum Zitat Bhattacharyya S, Sen P, Wallet M, Long B, Baldwin AS Jr, Tisch R. Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of IkappaB kinase activity. Blood. 2004;104(4):1100–9.PubMedCrossRef Bhattacharyya S, Sen P, Wallet M, Long B, Baldwin AS Jr, Tisch R. Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of IkappaB kinase activity. Blood. 2004;104(4):1100–9.PubMedCrossRef
5.
Zurück zum Zitat Foey AD, Feldmann M, Brennan FM. CD40 ligation induces macrophage IL-10 and TNF-alpha production: differential use of the PI3K and p42/44 MAPK-pathways. Cytokine. 2001;16(4):131–42.PubMedCrossRef Foey AD, Feldmann M, Brennan FM. CD40 ligation induces macrophage IL-10 and TNF-alpha production: differential use of the PI3K and p42/44 MAPK-pathways. Cytokine. 2001;16(4):131–42.PubMedCrossRef
6.
Zurück zum Zitat Frossi B, Rivera J, Hirsch E, Pucillo C. Selective activation of Fyn/PI3K and p38 MAPK regulates IL-4 production in BMMC under nontoxic stress condition. J Immunol. 2007;178(4):2549–55.PubMed Frossi B, Rivera J, Hirsch E, Pucillo C. Selective activation of Fyn/PI3K and p38 MAPK regulates IL-4 production in BMMC under nontoxic stress condition. J Immunol. 2007;178(4):2549–55.PubMed
7.
Zurück zum Zitat Fukao T, Tanabe M, Terauchi Y, Ota T, Matsuda S, Asano T, Kadowaki T, Takeuchi T, Koyasu S. PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat Immunol. 2002;3(9):875–81.PubMedCrossRef Fukao T, Tanabe M, Terauchi Y, Ota T, Matsuda S, Asano T, Kadowaki T, Takeuchi T, Koyasu S. PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat Immunol. 2002;3(9):875–81.PubMedCrossRef
8.
Zurück zum Zitat Neves BM, Cruz MT, Francisco V, Garcia-Rodriguez C, Silvestre R, Cordeiro-da-Silva A, Dinis AM, Batista MT, Duarte CB, Lopes MC. Differential roles of PI3-Kinase, MAPKs and NF-kappaB on the manipulation of dendritic cell T(h)1/T(h)2 cytokine/chemokine polarizing profile. Mol Immunol. 2009;46(13):2481–92.PubMedCrossRef Neves BM, Cruz MT, Francisco V, Garcia-Rodriguez C, Silvestre R, Cordeiro-da-Silva A, Dinis AM, Batista MT, Duarte CB, Lopes MC. Differential roles of PI3-Kinase, MAPKs and NF-kappaB on the manipulation of dendritic cell T(h)1/T(h)2 cytokine/chemokine polarizing profile. Mol Immunol. 2009;46(13):2481–92.PubMedCrossRef
9.
Zurück zum Zitat Okkenhaug K, Vanhaesebroeck B. PI3K in lymphocyte development, differentiation and activation. Nat Rev. 2003;3(4):317–30.CrossRef Okkenhaug K, Vanhaesebroeck B. PI3K in lymphocyte development, differentiation and activation. Nat Rev. 2003;3(4):317–30.CrossRef
10.
Zurück zum Zitat Patel RK, Mohan C. PI3K/AKT signaling and systemic autoimmunity. Immunol Res. 2005;31(1):47–55.PubMedCrossRef Patel RK, Mohan C. PI3K/AKT signaling and systemic autoimmunity. Immunol Res. 2005;31(1):47–55.PubMedCrossRef
11.
Zurück zum Zitat Weichhart T, Saemann MD. The PI3K/Akt/mTOR pathway in innate immune cells: emerging therapeutic applications. Ann Rheum Dis. 2008;67(Suppl 3):iii70–4.PubMedCrossRef Weichhart T, Saemann MD. The PI3K/Akt/mTOR pathway in innate immune cells: emerging therapeutic applications. Ann Rheum Dis. 2008;67(Suppl 3):iii70–4.PubMedCrossRef
12.
Zurück zum Zitat Harris SJ, Foster JG, Ward SG. PI3K isoforms as drug targets in inflammatory diseases: lessons from pharmacological and genetic strategies. Curr Opin Investig Drugs. 2009;10(11):1151–62.PubMed Harris SJ, Foster JG, Ward SG. PI3K isoforms as drug targets in inflammatory diseases: lessons from pharmacological and genetic strategies. Curr Opin Investig Drugs. 2009;10(11):1151–62.PubMed
13.
Zurück zum Zitat Caparros E, Munoz P, Sierra-Filardi E, Serrano-Gomez D, Puig-Kroger A, Rodriguez-Fernandez JL, Mellado M, Sancho J, Zubiaur M, Corbi AL. DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production. Blood. 2006;107(10):3950–8.PubMedCrossRef Caparros E, Munoz P, Sierra-Filardi E, Serrano-Gomez D, Puig-Kroger A, Rodriguez-Fernandez JL, Mellado M, Sancho J, Zubiaur M, Corbi AL. DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production. Blood. 2006;107(10):3950–8.PubMedCrossRef
14.
Zurück zum Zitat Guiducci C, Ghirelli C, Marloie-Provost MA, Matray T, Coffman RL, Liu YJ, Barrat FJ, Soumelis V. PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation. J Exp Med. 2008;205(2):315–22.PubMedCrossRef Guiducci C, Ghirelli C, Marloie-Provost MA, Matray T, Coffman RL, Liu YJ, Barrat FJ, Soumelis V. PI3K is critical for the nuclear translocation of IRF-7 and type I IFN production by human plasmacytoid predendritic cells in response to TLR activation. J Exp Med. 2008;205(2):315–22.PubMedCrossRef
15.
Zurück zum Zitat Karakhanova S, Meisel S, Ring S, Mahnke K, Enk AH. ERK/p38 MAP-kinases and PI3K are involved in the differential regulation of B7-H1 expression in DC subsets. Eur J Immunol. 2010;40(1):254–66.PubMedCrossRef Karakhanova S, Meisel S, Ring S, Mahnke K, Enk AH. ERK/p38 MAP-kinases and PI3K are involved in the differential regulation of B7-H1 expression in DC subsets. Eur J Immunol. 2010;40(1):254–66.PubMedCrossRef
16.
Zurück zum Zitat Xie J, Qian J, Yang J, Wang S, Freeman ME 3rd, Yi Q. Critical roles of Raf/MEK/ERK and PI3K/AKT signaling and inactivation of p38 MAP kinase in the differentiation and survival of monocyte-derived immature dendritic cells. Exp Hematol. 2005;33(5):564–72.PubMedCrossRef Xie J, Qian J, Yang J, Wang S, Freeman ME 3rd, Yi Q. Critical roles of Raf/MEK/ERK and PI3K/AKT signaling and inactivation of p38 MAP kinase in the differentiation and survival of monocyte-derived immature dendritic cells. Exp Hematol. 2005;33(5):564–72.PubMedCrossRef
17.
Zurück zum Zitat Fukao T, Koyasu S. PI3K and negative regulation of TLR signaling. Trends Immunol. 2003;24(7):358–63.PubMedCrossRef Fukao T, Koyasu S. PI3K and negative regulation of TLR signaling. Trends Immunol. 2003;24(7):358–63.PubMedCrossRef
18.
Zurück zum Zitat An H, Yu Y, Zhang M, Xu H, Qi R, Yan X, Liu S, Wang W, Guo Z, Guo J, et al. Involvement of ERK, p38 and NF-kappaB signal transduction in regulation of TLR2, TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic cells. Immunology. 2002;106(1):38–45.PubMedCrossRef An H, Yu Y, Zhang M, Xu H, Qi R, Yan X, Liu S, Wang W, Guo Z, Guo J, et al. Involvement of ERK, p38 and NF-kappaB signal transduction in regulation of TLR2, TLR4 and TLR9 gene expression induced by lipopolysaccharide in mouse dendritic cells. Immunology. 2002;106(1):38–45.PubMedCrossRef
19.
Zurück zum Zitat Kumagai Y, Takeuchi O, Akira S. TLR9 as a key receptor for the recognition of DNA. Adv Drug Deliv Rev. 2008;60(7):795–804.PubMedCrossRef Kumagai Y, Takeuchi O, Akira S. TLR9 as a key receptor for the recognition of DNA. Adv Drug Deliv Rev. 2008;60(7):795–804.PubMedCrossRef
20.
Zurück zum Zitat Mitchell D, Olive C. Regulation of toll-like receptor-induced chemokine production in murine dendritic cells by mitogen-activated protein kinases. Mol Immunol. 2010;47(11–12):2065–73.PubMedCrossRef Mitchell D, Olive C. Regulation of toll-like receptor-induced chemokine production in murine dendritic cells by mitogen-activated protein kinases. Mol Immunol. 2010;47(11–12):2065–73.PubMedCrossRef
21.
Zurück zum Zitat Ruse M, Knaus UG. New players in TLR-mediated innate immunity: PI3K and small Rho GTPases. Immunol Res. 2006;34(1):33–48.PubMedCrossRef Ruse M, Knaus UG. New players in TLR-mediated innate immunity: PI3K and small Rho GTPases. Immunol Res. 2006;34(1):33–48.PubMedCrossRef
22.
Zurück zum Zitat Wohlfert EA, Clark RB. ‘Vive la resistance!’—the PI3K-Akt pathway can determine target sensitivity to regulatory T cell suppression. Trends Immunol. 2007;28(4):154–60.PubMedCrossRef Wohlfert EA, Clark RB. ‘Vive la resistance!’—the PI3K-Akt pathway can determine target sensitivity to regulatory T cell suppression. Trends Immunol. 2007;28(4):154–60.PubMedCrossRef
23.
Zurück zum Zitat Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245–52.PubMedCrossRef Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245–52.PubMedCrossRef
24.
Zurück zum Zitat Lutz MB, Schuler G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol. 2002;23(9):445–9.PubMedCrossRef Lutz MB, Schuler G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol. 2002;23(9):445–9.PubMedCrossRef
25.
Zurück zum Zitat Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol. 2003;21:685–711.PubMedCrossRef Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol. 2003;21:685–711.PubMedCrossRef
26.
Zurück zum Zitat Vlad G, Cortesini R, Suciu-Foca N. License to heal: bidirectional interaction of antigen-specific regulatory T cells and tolerogenic APC. J Immunol. 2005;174(10):5907–14.PubMed Vlad G, Cortesini R, Suciu-Foca N. License to heal: bidirectional interaction of antigen-specific regulatory T cells and tolerogenic APC. J Immunol. 2005;174(10):5907–14.PubMed
27.
Zurück zum Zitat Nikolic T, Welzen-Coppens JM, Leenen PJ, Drexhage HA, Versnel MA. Plasmacytoid dendritic cells in autoimmune diabetes—potential tools for immunotherapy. Immunobiology. 2009;214(9–10):791–9.PubMedCrossRef Nikolic T, Welzen-Coppens JM, Leenen PJ, Drexhage HA, Versnel MA. Plasmacytoid dendritic cells in autoimmune diabetes—potential tools for immunotherapy. Immunobiology. 2009;214(9–10):791–9.PubMedCrossRef
28.
Zurück zum Zitat Kalinski P. Dendritic cells in immunotherapy of established cancer: roles of signals 1, 2, 3 and 4. Curr Opin Investig Drugs. 2009;10(6):526–35.PubMed Kalinski P. Dendritic cells in immunotherapy of established cancer: roles of signals 1, 2, 3 and 4. Curr Opin Investig Drugs. 2009;10(6):526–35.PubMed
29.
30.
Zurück zum Zitat Nencioni A, Grunebach F, Schmidt SM, Muller MR, Boy D, Patrone F, Ballestrero A, Brossart P. The use of dendritic cells in cancer immunotherapy. Crit Rev Oncol Hematol. 2008;65(3):191–9.PubMedCrossRef Nencioni A, Grunebach F, Schmidt SM, Muller MR, Boy D, Patrone F, Ballestrero A, Brossart P. The use of dendritic cells in cancer immunotherapy. Crit Rev Oncol Hematol. 2008;65(3):191–9.PubMedCrossRef
31.
Zurück zum Zitat Kornbluth RS, Stone GW. Immunostimulatory combinations: designing the next generation of vaccine adjuvants. J Leukoc Biol. 2006;80(5):1084–102.PubMedCrossRef Kornbluth RS, Stone GW. Immunostimulatory combinations: designing the next generation of vaccine adjuvants. J Leukoc Biol. 2006;80(5):1084–102.PubMedCrossRef
32.
Zurück zum Zitat Mahnke K, Schmitt E, Bonifaz L, Enk AH, Jonuleit H. Immature, but not inactive: the tolerogenic function of immature dendritic cells. Immunol Cell Biol. 2002;80(5):477–83.PubMedCrossRef Mahnke K, Schmitt E, Bonifaz L, Enk AH, Jonuleit H. Immature, but not inactive: the tolerogenic function of immature dendritic cells. Immunol Cell Biol. 2002;80(5):477–83.PubMedCrossRef
33.
Zurück zum Zitat Nouri-Shirazi M, Thomson AW. Dendritic cells as promoters of transplant tolerance. Expert Opin Biol Ther. 2006;6(4):325–39.PubMedCrossRef Nouri-Shirazi M, Thomson AW. Dendritic cells as promoters of transplant tolerance. Expert Opin Biol Ther. 2006;6(4):325–39.PubMedCrossRef
34.
Zurück zum Zitat Bottino R, Lemarchand P, Trucco M, Giannoukakis N. Gene- and cell-based therapeutics for type I diabetes mellitus. Gene Ther. 2003;10(10):875–89.PubMedCrossRef Bottino R, Lemarchand P, Trucco M, Giannoukakis N. Gene- and cell-based therapeutics for type I diabetes mellitus. Gene Ther. 2003;10(10):875–89.PubMedCrossRef
35.
Zurück zum Zitat Chen D, Sung R, Bromberg JS. Gene therapy in transplantation. Transpl Immunol. 2002;9(2–4):301–14.PubMedCrossRef Chen D, Sung R, Bromberg JS. Gene therapy in transplantation. Transpl Immunol. 2002;9(2–4):301–14.PubMedCrossRef
36.
37.
Zurück zum Zitat Tarner IH, Slavin AJ, McBride J, Levicnik A, Smith R, Nolan GP, Contag CH, Fathman CG. Treatment of autoimmune disease by adoptive cellular gene therapy. Ann N Y Acad Sci. 2003;998:512–9.PubMedCrossRef Tarner IH, Slavin AJ, McBride J, Levicnik A, Smith R, Nolan GP, Contag CH, Fathman CG. Treatment of autoimmune disease by adoptive cellular gene therapy. Ann N Y Acad Sci. 2003;998:512–9.PubMedCrossRef
38.
Zurück zum Zitat Trucco M, Robbins PD, Thomson AW, Giannoukakis N. Gene therapy strategies to prevent autoimmune disorders. Curr Gene Ther. 2002;2(3):341–54.PubMedCrossRef Trucco M, Robbins PD, Thomson AW, Giannoukakis N. Gene therapy strategies to prevent autoimmune disorders. Curr Gene Ther. 2002;2(3):341–54.PubMedCrossRef
39.
Zurück zum Zitat Chen W. Dendritic cells and (CD4+)CD25+ T regulatory cells: crosstalk between two professionals in immunity versus tolerance. Front Biosci. 2006;11:1360–70.PubMedCrossRef Chen W. Dendritic cells and (CD4+)CD25+ T regulatory cells: crosstalk between two professionals in immunity versus tolerance. Front Biosci. 2006;11:1360–70.PubMedCrossRef
40.
Zurück zum Zitat Hugues S, Boissonnas A, Amigorena S, Fetler L. The dynamics of dendritic cell-T cell interactions in priming and tolerance. Curr Opin Immunol. 2006;18(4):491–5.PubMedCrossRef Hugues S, Boissonnas A, Amigorena S, Fetler L. The dynamics of dendritic cell-T cell interactions in priming and tolerance. Curr Opin Immunol. 2006;18(4):491–5.PubMedCrossRef
41.
Zurück zum Zitat Beissert S, Schwarz A, Schwarz T. Regulatory T cells. J Invest Dermatol. 2006;126(1):15–24.PubMedCrossRef Beissert S, Schwarz A, Schwarz T. Regulatory T cells. J Invest Dermatol. 2006;126(1):15–24.PubMedCrossRef
42.
Zurück zum Zitat Enk AH. DCs and cytokines cooperate for the induction of Tregs. Ernst Schering Res Found Workshop. 2006;56:97–106.PubMedCrossRef Enk AH. DCs and cytokines cooperate for the induction of Tregs. Ernst Schering Res Found Workshop. 2006;56:97–106.PubMedCrossRef
43.
Zurück zum Zitat Huber S, Schramm C. TGF-beta and CD4+ CD25+ regulatory T cells. Front Biosci. 2006;11:1014–23.PubMedCrossRef Huber S, Schramm C. TGF-beta and CD4+ CD25+ regulatory T cells. Front Biosci. 2006;11:1014–23.PubMedCrossRef
44.
Zurück zum Zitat Lohr J, Knoechel B, Abbas AK. Regulatory T cells in the periphery. Immunol Rev. 2006;212:149–62.PubMedCrossRef Lohr J, Knoechel B, Abbas AK. Regulatory T cells in the periphery. Immunol Rev. 2006;212:149–62.PubMedCrossRef
45.
Zurück zum Zitat Roncarolo MG, Gregori S, Battaglia M, Bacchetta R, Fleischhauer K, Levings MK. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol Rev. 2006;212:28–50.PubMedCrossRef Roncarolo MG, Gregori S, Battaglia M, Bacchetta R, Fleischhauer K, Levings MK. Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunol Rev. 2006;212:28–50.PubMedCrossRef
46.
Zurück zum Zitat Shevach EM, DiPaolo RA, Andersson J, Zhao DM, Stephens GL, Thornton AM. The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells. Immunol Rev. 2006;212:60–73.PubMedCrossRef Shevach EM, DiPaolo RA, Andersson J, Zhao DM, Stephens GL, Thornton AM. The lifestyle of naturally occurring CD4+ CD25+ Foxp3+ regulatory T cells. Immunol Rev. 2006;212:60–73.PubMedCrossRef
47.
Zurück zum Zitat Tang Q, Bluestone JA. Regulatory T-cell physiology and application to treat autoimmunity. Immunol Rev. 2006;212:217–37.PubMedCrossRef Tang Q, Bluestone JA. Regulatory T-cell physiology and application to treat autoimmunity. Immunol Rev. 2006;212:217–37.PubMedCrossRef
48.
Zurück zum Zitat Verhagen J, Blaser K, Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy: T-regulatory cells and more. Immunol Allergy Clin North Am. 2006;26(2):207–31.PubMedCrossRef Verhagen J, Blaser K, Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy: T-regulatory cells and more. Immunol Allergy Clin North Am. 2006;26(2):207–31.PubMedCrossRef
49.
Zurück zum Zitat Zhang L, Yi H, Xia XP, Zhao Y. Transforming growth factor-beta: an important role in CD4+ CD25+ regulatory T cells and immune tolerance. Autoimmunity. 2006;39(4):269–76.PubMedCrossRef Zhang L, Yi H, Xia XP, Zhao Y. Transforming growth factor-beta: an important role in CD4+ CD25+ regulatory T cells and immune tolerance. Autoimmunity. 2006;39(4):269–76.PubMedCrossRef
50.
Zurück zum Zitat Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, et al. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science. 2002;297(5588):1867–70.PubMedCrossRef Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, et al. Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science. 2002;297(5588):1867–70.PubMedCrossRef
51.
Zurück zum Zitat Mellor AL, Chandler P, Baban B, Hansen AM, Marshall B, Pihkala J, Waldmann H, Cobbold S, Adams E, Munn DH. Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase. Int Immunol. 2004;16(10):1391–401.PubMedCrossRef Mellor AL, Chandler P, Baban B, Hansen AM, Marshall B, Pihkala J, Waldmann H, Cobbold S, Adams E, Munn DH. Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase. Int Immunol. 2004;16(10):1391–401.PubMedCrossRef
52.
Zurück zum Zitat Mellor AL, Munn DH. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol. 2004;4(10):762–74.PubMedCrossRef Mellor AL, Munn DH. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol. 2004;4(10):762–74.PubMedCrossRef
53.
Zurück zum Zitat Ahuja SS. In vitro generation of functional human and murine dendritic cells. Methods Mol Biol (Clifton, NJ). 2001;156:67–77. Ahuja SS. In vitro generation of functional human and murine dendritic cells. Methods Mol Biol (Clifton, NJ). 2001;156:67–77.
54.
Zurück zum Zitat Anton D, Dabadghao S, Palucka K, Holm G, Yi Q. Generation of dendritic cells from peripheral blood adherent cells in medium with human serum. Scand J Immunol. 1998;47(2):116–21.PubMedCrossRef Anton D, Dabadghao S, Palucka K, Holm G, Yi Q. Generation of dendritic cells from peripheral blood adherent cells in medium with human serum. Scand J Immunol. 1998;47(2):116–21.PubMedCrossRef
55.
Zurück zum Zitat Bernhard H, Disis ML, Heimfeld S, Hand S, Gralow JR, Cheever MA. Generation of immunostimulatory dendritic cells from human CD34+ hematopoietic progenitor cells of the bone marrow and peripheral blood. Cancer Res. 1995;55(5):1099–104.PubMed Bernhard H, Disis ML, Heimfeld S, Hand S, Gralow JR, Cheever MA. Generation of immunostimulatory dendritic cells from human CD34+ hematopoietic progenitor cells of the bone marrow and peripheral blood. Cancer Res. 1995;55(5):1099–104.PubMed
56.
Zurück zum Zitat Brossart P, Grunebach F, Stuhler G, Reichardt VL, Mohle R, Kanz L, Brugger W. Generation of functional human dendritic cells from adherent peripheral blood monocytes by CD40 ligation in the absence of granulocyte-macrophage colony-stimulating factor. Blood. 1998;92(11):4238–47.PubMed Brossart P, Grunebach F, Stuhler G, Reichardt VL, Mohle R, Kanz L, Brugger W. Generation of functional human dendritic cells from adherent peripheral blood monocytes by CD40 ligation in the absence of granulocyte-macrophage colony-stimulating factor. Blood. 1998;92(11):4238–47.PubMed
57.
Zurück zum Zitat Cao H, Verge V, Baron C, Martinache C, Leon A, Scholl S, Gorin NC, Salamero J, Assari S, Bernard J, et al. In vitro generation of dendritic cells from human blood monocytes in experimental conditions compatible for in vivo cell therapy. J Hematother Stem Cell Res. 2000;9(2):183–94.PubMedCrossRef Cao H, Verge V, Baron C, Martinache C, Leon A, Scholl S, Gorin NC, Salamero J, Assari S, Bernard J, et al. In vitro generation of dendritic cells from human blood monocytes in experimental conditions compatible for in vivo cell therapy. J Hematother Stem Cell Res. 2000;9(2):183–94.PubMedCrossRef
58.
Zurück zum Zitat Gluckman JC, Canque B, Chapuis F, Rosenzwajg M. In vitro generation of human dendritic cells and cell therapy. Cytokines Cell Mol Ther. 1997;3(3):187–96.PubMed Gluckman JC, Canque B, Chapuis F, Rosenzwajg M. In vitro generation of human dendritic cells and cell therapy. Cytokines Cell Mol Ther. 1997;3(3):187–96.PubMed
59.
Zurück zum Zitat Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, Muramatsu S, Steinman RM. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992;176(6):1693–702.PubMedCrossRef Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, Muramatsu S, Steinman RM. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992;176(6):1693–702.PubMedCrossRef
60.
Zurück zum Zitat Manca F, Li Pira G, Fenoglio D, Fang SP, Habeshaw A, Knight SC, Dalgleish AG. Dendritic cells are potent antigen-presenting cells for in vitro induction of primary human CD4+ T-cell lines specific for HIV gp120. J Acquir Immune Defic Syndr. 1994;7(1):15–23.PubMed Manca F, Li Pira G, Fenoglio D, Fang SP, Habeshaw A, Knight SC, Dalgleish AG. Dendritic cells are potent antigen-presenting cells for in vitro induction of primary human CD4+ T-cell lines specific for HIV gp120. J Acquir Immune Defic Syndr. 1994;7(1):15–23.PubMed
61.
Zurück zum Zitat Ratta M, Rondelli D, Fortuna A, Curti A, Fogli M, Fagnoni F, Martinelli G, Terragna C, Tura S, Lemoli RM. Generation and functional characterization of human dendritic cells derived from CD34 cells mobilized into peripheral blood: comparison with bone marrow CD34+ cells. Br J Haematol. 1998;101(4):756–65.PubMedCrossRef Ratta M, Rondelli D, Fortuna A, Curti A, Fogli M, Fagnoni F, Martinelli G, Terragna C, Tura S, Lemoli RM. Generation and functional characterization of human dendritic cells derived from CD34 cells mobilized into peripheral blood: comparison with bone marrow CD34+ cells. Br J Haematol. 1998;101(4):756–65.PubMedCrossRef
62.
Zurück zum Zitat Romani N, Reider D, Heuer M, Ebner S, Kampgen E, Eibl B, Niederwieser D, Schuler G. Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J Immunol Methods. 1996;196(2):137–51.PubMedCrossRef Romani N, Reider D, Heuer M, Ebner S, Kampgen E, Eibl B, Niederwieser D, Schuler G. Generation of mature dendritic cells from human blood. An improved method with special regard to clinical applicability. J Immunol Methods. 1996;196(2):137–51.PubMedCrossRef
63.
Zurück zum Zitat Arab S, Motamedi M, Khansari N, Moazzeni SM, Gheflati Z, Hadjati J. Dendritic cell maturation with CpG for tumor immunotherapy. Iran J Immunol. 2006;3(3):99–105.PubMed Arab S, Motamedi M, Khansari N, Moazzeni SM, Gheflati Z, Hadjati J. Dendritic cell maturation with CpG for tumor immunotherapy. Iran J Immunol. 2006;3(3):99–105.PubMed
64.
Zurück zum Zitat Iparraguirre A, Tobias JW, Hensley SE, Masek KS, Cavanagh LL, Rendl M, Hunter CA, Ertl HC, von Andrian UH, Weninger W. Two distinct activation states of plasmacytoid dendritic cells induced by influenza virus and CpG 1826 oligonucleotide. J Leukoc Biol. 2008;83(3):610–20.PubMedCrossRef Iparraguirre A, Tobias JW, Hensley SE, Masek KS, Cavanagh LL, Rendl M, Hunter CA, Ertl HC, von Andrian UH, Weninger W. Two distinct activation states of plasmacytoid dendritic cells induced by influenza virus and CpG 1826 oligonucleotide. J Leukoc Biol. 2008;83(3):610–20.PubMedCrossRef
65.
Zurück zum Zitat Lee KW, Kim DS, Kwon HJ. CG sequence- and phosphorothioate backbone modification-dependent activation of the NF-kappaB-responsive gene expression by CpG-oligodeoxynucleotides in human RPMI 8226 B cells. Mol Immunol. 2004;41(10):955–64.PubMed Lee KW, Kim DS, Kwon HJ. CG sequence- and phosphorothioate backbone modification-dependent activation of the NF-kappaB-responsive gene expression by CpG-oligodeoxynucleotides in human RPMI 8226 B cells. Mol Immunol. 2004;41(10):955–64.PubMed
66.
Zurück zum Zitat Switaj T, Jalili A, Jakubowska AB, Drela N, Stoksik M, Nowis D, Basak G, Golab J, Wysocki PJ, Mackiewicz A, et al. CpG immunostimulatory oligodeoxynucleotide 1826 enhances antitumor effect of interleukin 12 gene-modified tumor vaccine in a melanoma model in mice. Clin Cancer Res. 2004;10(12 Pt 1):4165–75.PubMedCrossRef Switaj T, Jalili A, Jakubowska AB, Drela N, Stoksik M, Nowis D, Basak G, Golab J, Wysocki PJ, Mackiewicz A, et al. CpG immunostimulatory oligodeoxynucleotide 1826 enhances antitumor effect of interleukin 12 gene-modified tumor vaccine in a melanoma model in mice. Clin Cancer Res. 2004;10(12 Pt 1):4165–75.PubMedCrossRef
67.
Zurück zum Zitat Giannoukakis N, Bonham CA, Qian S, Zhou Z, Peng L, Harnaha J, Li W, Thomson AW, Fung JJ, Robbins PD, et al. Prolongation of cardiac allograft survival using dendritic cells treated with NF-kB decoy oligodeoxyribonucleotides. Mol Ther. 2000;1(5 Pt 1):430–7. (in process citation).PubMedCrossRef Giannoukakis N, Bonham CA, Qian S, Zhou Z, Peng L, Harnaha J, Li W, Thomson AW, Fung JJ, Robbins PD, et al. Prolongation of cardiac allograft survival using dendritic cells treated with NF-kB decoy oligodeoxyribonucleotides. Mol Ther. 2000;1(5 Pt 1):430–7. (in process citation).PubMedCrossRef
68.
Zurück zum Zitat Machen J, Harnaha J, Lakomy R, Styche A, Trucco M, Giannoukakis N. Antisense oligonucleotides down-regulating costimulation confer diabetes-preventive properties to nonobese diabetic mouse dendritic cells. J Immunol. 2004;173(7):4331–41.PubMed Machen J, Harnaha J, Lakomy R, Styche A, Trucco M, Giannoukakis N. Antisense oligonucleotides down-regulating costimulation confer diabetes-preventive properties to nonobese diabetic mouse dendritic cells. J Immunol. 2004;173(7):4331–41.PubMed
69.
Zurück zum Zitat Adorini L, Giarratana N, Penna G. Pharmacological induction of tolerogenic dendritic cells and regulatory T cells. Semin Immunol. 2004;16(2):127–34.PubMedCrossRef Adorini L, Giarratana N, Penna G. Pharmacological induction of tolerogenic dendritic cells and regulatory T cells. Semin Immunol. 2004;16(2):127–34.PubMedCrossRef
70.
Zurück zum Zitat Thomson AW, Robbins PD. Tolerogenic dendritic cells for autoimmune disease and transplantation. Ann Rheum Dis. 2008;67(Suppl 3):iii90–6.PubMedCrossRef Thomson AW, Robbins PD. Tolerogenic dendritic cells for autoimmune disease and transplantation. Ann Rheum Dis. 2008;67(Suppl 3):iii90–6.PubMedCrossRef
71.
Zurück zum Zitat Antignano F, Ibaraki M, Ruschmann J, Jagdeo J, Krystal G. SHIP negatively regulates Flt3L-derived dendritic cell generation and positively regulates MyD88-independent TLR-induced maturation. J Leukoc Biol. Antignano F, Ibaraki M, Ruschmann J, Jagdeo J, Krystal G. SHIP negatively regulates Flt3L-derived dendritic cell generation and positively regulates MyD88-independent TLR-induced maturation. J Leukoc Biol.
72.
Zurück zum Zitat Antignano F, Ibaraki M, Kim C, Ruschmann J, Zhang A, Helgason CD, Krystal G. SHIP is required for dendritic cell maturation. J Immunol. 2010;184(6):2805–13.PubMedCrossRef Antignano F, Ibaraki M, Kim C, Ruschmann J, Zhang A, Helgason CD, Krystal G. SHIP is required for dendritic cell maturation. J Immunol. 2010;184(6):2805–13.PubMedCrossRef
73.
Zurück zum Zitat van de Laar L, Buitenhuis M, Wensveen FM, Janssen HL, Coffer PJ, Woltman AM. Human CD34-derived myeloid dendritic cell development requires intact phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin signaling. J Immunol. 2010;184(12):6600–11.PubMedCrossRef van de Laar L, Buitenhuis M, Wensveen FM, Janssen HL, Coffer PJ, Woltman AM. Human CD34-derived myeloid dendritic cell development requires intact phosphatidylinositol 3-kinase-protein kinase B-mammalian target of rapamycin signaling. J Immunol. 2010;184(12):6600–11.PubMedCrossRef
74.
Zurück zum Zitat Lo AS, Gorak-Stolinska P, Bachy V, Ibrahim MA, Kemeny DM, Maher J. Modulation of dendritic cell differentiation by colony-stimulating factor-1: role of phosphatidylinositol 3′-kinase and delayed caspase activation. J Leukoc Biol. 2007;82(6):1446–54.PubMedCrossRef Lo AS, Gorak-Stolinska P, Bachy V, Ibrahim MA, Kemeny DM, Maher J. Modulation of dendritic cell differentiation by colony-stimulating factor-1: role of phosphatidylinositol 3′-kinase and delayed caspase activation. J Leukoc Biol. 2007;82(6):1446–54.PubMedCrossRef
75.
Zurück zum Zitat Kramer PR, Winger V, Reuben J. PI3K limits TNF-alpha production in CD16-activated monocytes. Eur J Immunol. 2009;39(2):561–70.PubMedCrossRef Kramer PR, Winger V, Reuben J. PI3K limits TNF-alpha production in CD16-activated monocytes. Eur J Immunol. 2009;39(2):561–70.PubMedCrossRef
76.
Zurück zum Zitat Fu F, Li Y, Qian S, Lu L, Chambers F, Starzl TE, Fung JJ, Thomson AW. Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80dim, CD86−) prolong cardiac allograft survival in nonimmunosuppressed recipients. Transplantation. 1996;62(5):659–65.PubMedCrossRef Fu F, Li Y, Qian S, Lu L, Chambers F, Starzl TE, Fung JJ, Thomson AW. Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80dim, CD86−) prolong cardiac allograft survival in nonimmunosuppressed recipients. Transplantation. 1996;62(5):659–65.PubMedCrossRef
77.
Zurück zum Zitat Lu L, Rudert WA, Qian S, McCaslin D, Fu F, Rao AS, Trucco M, Fung JJ, Starzl TE, Thomson AW. Growth of donor-derived dendritic cells from the bone marrow of murine liver allograft recipients in response to granulocyte/macrophage colony-stimulating factor. J Exp Med. 1995;182(2):379–87.PubMedCrossRef Lu L, Rudert WA, Qian S, McCaslin D, Fu F, Rao AS, Trucco M, Fung JJ, Starzl TE, Thomson AW. Growth of donor-derived dendritic cells from the bone marrow of murine liver allograft recipients in response to granulocyte/macrophage colony-stimulating factor. J Exp Med. 1995;182(2):379–87.PubMedCrossRef
78.
Zurück zum Zitat Shumilina E, Zahir N, Xuan NT, Lang F. Phosphoinositide 3-kinase dependent regulation of Kv channels in dendritic cells. Cell Physiol Biochem. 2007;20(6):801–8.PubMedCrossRef Shumilina E, Zahir N, Xuan NT, Lang F. Phosphoinositide 3-kinase dependent regulation of Kv channels in dendritic cells. Cell Physiol Biochem. 2007;20(6):801–8.PubMedCrossRef
79.
Zurück zum Zitat Aksoy E, Vanden Berghe W, Detienne S, Amraoui Z, Fitzgerald KA, Haegeman G, Goldman M, Willems F. Inhibition of phosphoinositide 3-kinase enhances TRIF-dependent NF-kappa B activation and IFN-beta synthesis downstream of toll-like receptor 3 and 4. Eur J Immunol. 2005;35(7):2200–9.PubMedCrossRef Aksoy E, Vanden Berghe W, Detienne S, Amraoui Z, Fitzgerald KA, Haegeman G, Goldman M, Willems F. Inhibition of phosphoinositide 3-kinase enhances TRIF-dependent NF-kappa B activation and IFN-beta synthesis downstream of toll-like receptor 3 and 4. Eur J Immunol. 2005;35(7):2200–9.PubMedCrossRef
80.
Zurück zum Zitat Liu E, Law HK, Lau YL. Insulin-like growth factor I promotes maturation and inhibits apoptosis of immature cord blood monocyte-derived dendritic cells through MEK and PI 3-kinase pathways. Pediatr Res. 2003;54(6):919–25.PubMedCrossRef Liu E, Law HK, Lau YL. Insulin-like growth factor I promotes maturation and inhibits apoptosis of immature cord blood monocyte-derived dendritic cells through MEK and PI 3-kinase pathways. Pediatr Res. 2003;54(6):919–25.PubMedCrossRef
81.
Zurück zum Zitat Bhattacharya P, Gopisetty A, Ganesh BB, Sheng JR, Prabhakar BS. GM-CSF-induced, bone-marrow-derived dendritic cells can expand natural Tregs and induce adaptive Tregs by different mechanisms. J Leukoc Biol. 2010. Bhattacharya P, Gopisetty A, Ganesh BB, Sheng JR, Prabhakar BS. GM-CSF-induced, bone-marrow-derived dendritic cells can expand natural Tregs and induce adaptive Tregs by different mechanisms. J Leukoc Biol. 2010.
82.
Zurück zum Zitat Li H, Zhang GX, Chen Y, Xu H, Fitzgerald DC, Zhao Z, Rostami A. CD11c+ CD11b+ dendritic cells play an important role in intravenous tolerance and the suppression of experimental autoimmune encephalomyelitis. J Immunol. 2008;181(4):2483–93.PubMed Li H, Zhang GX, Chen Y, Xu H, Fitzgerald DC, Zhao Z, Rostami A. CD11c+ CD11b+ dendritic cells play an important role in intravenous tolerance and the suppression of experimental autoimmune encephalomyelitis. J Immunol. 2008;181(4):2483–93.PubMed
83.
Zurück zum Zitat Liu Q, Zhang C, Sun A, Zheng Y, Wang L, Cao X. Tumor-educated CD11bhighIalow regulatory dendritic cells suppress T cell response through arginase I. J Immunol. 2009;182(10):6207–16.PubMedCrossRef Liu Q, Zhang C, Sun A, Zheng Y, Wang L, Cao X. Tumor-educated CD11bhighIalow regulatory dendritic cells suppress T cell response through arginase I. J Immunol. 2009;182(10):6207–16.PubMedCrossRef
84.
Zurück zum Zitat Cobbold SP. T cell tolerance in transplantation: possibilities for therapeutic intervention. Expert Opin Ther Targets. 2002;6(5):583–99.PubMedCrossRef Cobbold SP. T cell tolerance in transplantation: possibilities for therapeutic intervention. Expert Opin Ther Targets. 2002;6(5):583–99.PubMedCrossRef
85.
Zurück zum Zitat Hochweller K, Anderton SM. Kinetics of costimulatory molecule expression by T cells and dendritic cells during the induction of tolerance versus immunity in vivo. Eur J Immunol. 2005;35(4):1086–96.PubMedCrossRef Hochweller K, Anderton SM. Kinetics of costimulatory molecule expression by T cells and dendritic cells during the induction of tolerance versus immunity in vivo. Eur J Immunol. 2005;35(4):1086–96.PubMedCrossRef
86.
Zurück zum Zitat Chhabra A, Chakraborty NG, Mukherji B. Silencing of endogenous IL-10 in human dendritic cells leads to the generation of an improved CTL response against human melanoma associated antigenic epitope, MART-1 27-35. Clin Immunol. 2008;126(3):251–9.PubMedCrossRef Chhabra A, Chakraborty NG, Mukherji B. Silencing of endogenous IL-10 in human dendritic cells leads to the generation of an improved CTL response against human melanoma associated antigenic epitope, MART-1 27-35. Clin Immunol. 2008;126(3):251–9.PubMedCrossRef
87.
Zurück zum Zitat Gundacker NC, Haudek VJ, Wimmer H, Slany A, Griss J, Bochkov V, Zielinski C, Wagner O, Stockl J, Gerner C. Cytoplasmic proteome and secretome profiles of differently stimulated human dendritic cells. J Proteome Res. 2009;8(6):2799–811.PubMedCrossRef Gundacker NC, Haudek VJ, Wimmer H, Slany A, Griss J, Bochkov V, Zielinski C, Wagner O, Stockl J, Gerner C. Cytoplasmic proteome and secretome profiles of differently stimulated human dendritic cells. J Proteome Res. 2009;8(6):2799–811.PubMedCrossRef
88.
Zurück zum Zitat Kwan WH, Boix C, Gougelet N, Fridman WH, Mueller CG. LPS induces rapid IL-10 release by M-CSF-conditioned tolerogenic dendritic cell precursors. J Leukoc Biol. 2007;82(1):133–41.PubMedCrossRef Kwan WH, Boix C, Gougelet N, Fridman WH, Mueller CG. LPS induces rapid IL-10 release by M-CSF-conditioned tolerogenic dendritic cell precursors. J Leukoc Biol. 2007;82(1):133–41.PubMedCrossRef
89.
Zurück zum Zitat Mnasria K, Lagaraine C, Manaa J, Lebranchu Y, Oueslati R. Anti CD25 treatment of human dendritic cells modulates both their cytokine synthesis profiles and their capacity to activate allogeneic CD4 T cells: a potential tolerogenic effect. Int Immunopharmacol. 2008;8(3):414–22.PubMedCrossRef Mnasria K, Lagaraine C, Manaa J, Lebranchu Y, Oueslati R. Anti CD25 treatment of human dendritic cells modulates both their cytokine synthesis profiles and their capacity to activate allogeneic CD4 T cells: a potential tolerogenic effect. Int Immunopharmacol. 2008;8(3):414–22.PubMedCrossRef
90.
Zurück zum Zitat Ureta G, Osorio F, Morales J, Rosemblatt M, Bono MR, Fierro JA. Generation of dendritic cells with regulatory properties. Transpl Proc. 2007;39(3):633–7.CrossRef Ureta G, Osorio F, Morales J, Rosemblatt M, Bono MR, Fierro JA. Generation of dendritic cells with regulatory properties. Transpl Proc. 2007;39(3):633–7.CrossRef
91.
Zurück zum Zitat Crane IJ, Forrester JV. Th1 and Th2 lymphocytes in autoimmune disease. Crit Rev Immunol. 2005;25(2):75–102.PubMedCrossRef Crane IJ, Forrester JV. Th1 and Th2 lymphocytes in autoimmune disease. Crit Rev Immunol. 2005;25(2):75–102.PubMedCrossRef
92.
Zurück zum Zitat Kutlu A, Bozkurt B, Ciftci F, Bozkanat E. Th1-Th2 interaction: is more complex than a see-saw? Scand J Immunol. 2007;65(4):393–5.PubMedCrossRef Kutlu A, Bozkurt B, Ciftci F, Bozkanat E. Th1-Th2 interaction: is more complex than a see-saw? Scand J Immunol. 2007;65(4):393–5.PubMedCrossRef
93.
Zurück zum Zitat Moss RB, Moll T, El-Kalay M, Kohne C, Soo Hoo W, Encinas J, Carlo DJ. Th1/Th2 cells in inflammatory disease states: therapeutic implications. Exp Opin Biol Ther. 2004;4(12):1887–96.CrossRef Moss RB, Moll T, El-Kalay M, Kohne C, Soo Hoo W, Encinas J, Carlo DJ. Th1/Th2 cells in inflammatory disease states: therapeutic implications. Exp Opin Biol Ther. 2004;4(12):1887–96.CrossRef
94.
Zurück zum Zitat Pirenne J, Kitade H, Kawai M, Koshiba T, Van Damme B, Mathieu C, Waer M. Regulatory cells, TH1/TH2 unbalance, and antibody-induced chronic rejection in operational tolerance induced by donor-specific blood transfusion. Transplantation. 2005;79(3 Suppl):S25–7.PubMedCrossRef Pirenne J, Kitade H, Kawai M, Koshiba T, Van Damme B, Mathieu C, Waer M. Regulatory cells, TH1/TH2 unbalance, and antibody-induced chronic rejection in operational tolerance induced by donor-specific blood transfusion. Transplantation. 2005;79(3 Suppl):S25–7.PubMedCrossRef
95.
Zurück zum Zitat Utsugi M, Dobashi K, Ono A, Ishizuka T, Matsuzaki S, Hisada T, Shimizu Y, Kawata T, Aoki H, Kamide Y, et al. PI3K p110beta positively regulates lipopolysaccharide-induced IL-12 production in human macrophages and dendritic cells and JNK1 plays a novel role. J Immunol. 2009;182(9):5225–31.PubMedCrossRef Utsugi M, Dobashi K, Ono A, Ishizuka T, Matsuzaki S, Hisada T, Shimizu Y, Kawata T, Aoki H, Kamide Y, et al. PI3K p110beta positively regulates lipopolysaccharide-induced IL-12 production in human macrophages and dendritic cells and JNK1 plays a novel role. J Immunol. 2009;182(9):5225–31.PubMedCrossRef
96.
Zurück zum Zitat Kamda JD, Singer SM. Phosphoinositide 3-kinase-dependent inhibition of dendritic cell interleukin-12 production by Giardia lamblia. Infect Immun. 2009;77(2):685–93.PubMedCrossRef Kamda JD, Singer SM. Phosphoinositide 3-kinase-dependent inhibition of dendritic cell interleukin-12 production by Giardia lamblia. Infect Immun. 2009;77(2):685–93.PubMedCrossRef
97.
Zurück zum Zitat Ohtani M, Nagai S, Kondo S, Mizuno S, Nakamura K, Tanabe M, Takeuchi T, Matsuda S, Koyasu S. Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharide-induced interleukin-12 production in dendritic cells. Blood. 2008;112(3):635–43.PubMedCrossRef Ohtani M, Nagai S, Kondo S, Mizuno S, Nakamura K, Tanabe M, Takeuchi T, Matsuda S, Koyasu S. Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharide-induced interleukin-12 production in dendritic cells. Blood. 2008;112(3):635–43.PubMedCrossRef
98.
Zurück zum Zitat Agrawal A, Agrawal S, Cao JN, Su H, Osann K, Gupta S. Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway. J Immunol. 2007;178(11):6912–22.PubMed Agrawal A, Agrawal S, Cao JN, Su H, Osann K, Gupta S. Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway. J Immunol. 2007;178(11):6912–22.PubMed
99.
Zurück zum Zitat Vollmer J. Progress in drug development of immunostimulatory CpG oligodeoxynucleotide ligands for TLR9. Exp Opin Biol Ther. 2005;5(5):673–82.CrossRef Vollmer J. Progress in drug development of immunostimulatory CpG oligodeoxynucleotide ligands for TLR9. Exp Opin Biol Ther. 2005;5(5):673–82.CrossRef
100.
Zurück zum Zitat Martin M, Rehani K, Jope RS, Michalek SM. Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol. 2005;6(8):777–84.PubMedCrossRef Martin M, Rehani K, Jope RS, Michalek SM. Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol. 2005;6(8):777–84.PubMedCrossRef
101.
Zurück zum Zitat Pan K, Wang H, Liu WL, Zhang HK, Zhou J, Li JJ, Weng DS, Huang W, Sun JC, Liang XT, et al. The pivotal role of p38 and NF-kappaB signal pathways in the maturation of human monocyte-derived dendritic cells stimulated by streptococcal agent OK-432. Immunobiology. 2009;214(5):350–8.PubMedCrossRef Pan K, Wang H, Liu WL, Zhang HK, Zhou J, Li JJ, Weng DS, Huang W, Sun JC, Liang XT, et al. The pivotal role of p38 and NF-kappaB signal pathways in the maturation of human monocyte-derived dendritic cells stimulated by streptococcal agent OK-432. Immunobiology. 2009;214(5):350–8.PubMedCrossRef
102.
Zurück zum Zitat Trompezinski S, Migdal C, Tailhardat M, Le Varlet B, Courtellemont P, Haftek M, Serres M. Characterization of early events involved in human dendritic cell maturation induced by sensitizers: cross talk between MAPK signalling pathways. Toxicol Appl Pharmacol. 2008;230(3):397–406.PubMedCrossRef Trompezinski S, Migdal C, Tailhardat M, Le Varlet B, Courtellemont P, Haftek M, Serres M. Characterization of early events involved in human dendritic cell maturation induced by sensitizers: cross talk between MAPK signalling pathways. Toxicol Appl Pharmacol. 2008;230(3):397–406.PubMedCrossRef
103.
Zurück zum Zitat Luft T, Rodionova E, Maraskovsky E, Kirsch M, Hess M, Buchholtz C, Goerner M, Schnurr M, Skoda R, Ho AD. Adaptive functional differentiation of dendritic cells: integrating the network of extra- and intracellular signals. Blood. 2006;107(12):4763–9.PubMedCrossRef Luft T, Rodionova E, Maraskovsky E, Kirsch M, Hess M, Buchholtz C, Goerner M, Schnurr M, Skoda R, Ho AD. Adaptive functional differentiation of dendritic cells: integrating the network of extra- and intracellular signals. Blood. 2006;107(12):4763–9.PubMedCrossRef
104.
Zurück zum Zitat Nakahara T, Moroi Y, Uchi H, Furue M. Differential role of MAPK signaling in human dendritic cell maturation and Th1/Th2 engagement. J Dermatol Sci. 2006;42(1):1–11.PubMedCrossRef Nakahara T, Moroi Y, Uchi H, Furue M. Differential role of MAPK signaling in human dendritic cell maturation and Th1/Th2 engagement. J Dermatol Sci. 2006;42(1):1–11.PubMedCrossRef
105.
Zurück zum Zitat Hua F, Henstock PV, Tang B. ERK activation by GM-CSF reduces effectiveness of p38 inhibitor on inhibiting TNFalpha release. Int Immunopharmacol. 2010;10(7):730–7.PubMedCrossRef Hua F, Henstock PV, Tang B. ERK activation by GM-CSF reduces effectiveness of p38 inhibitor on inhibiting TNFalpha release. Int Immunopharmacol. 2010;10(7):730–7.PubMedCrossRef
106.
Zurück zum Zitat Lendemans S, Rani M, Selbach C, Kreuzfelder E, Schade FU, Flohe S. GM-CSF priming of human monocytes is dependent on ERK1/2 activation. J Endotoxin Res. 2006;12(1):10–20.PubMed Lendemans S, Rani M, Selbach C, Kreuzfelder E, Schade FU, Flohe S. GM-CSF priming of human monocytes is dependent on ERK1/2 activation. J Endotoxin Res. 2006;12(1):10–20.PubMed
107.
Zurück zum Zitat Nagafuchi S, Katsuta H, Ohno Y, Inoue Y, Shimoda K, Kogawa K, Ikeda Y, Koyanagi-Katsuta R, Yamasaki S, Tominaga H, et al. Mitogen-activated protein kinase pathway controls autoimmune regulator (AIRE) gene expression in granulo-monocyte colony stimulating factor (GM-CSF)-stimulated myelomonocytic leukemia OTC-4 cells. Immunol Lett. 2005;99(1):130–5.PubMedCrossRef Nagafuchi S, Katsuta H, Ohno Y, Inoue Y, Shimoda K, Kogawa K, Ikeda Y, Koyanagi-Katsuta R, Yamasaki S, Tominaga H, et al. Mitogen-activated protein kinase pathway controls autoimmune regulator (AIRE) gene expression in granulo-monocyte colony stimulating factor (GM-CSF)-stimulated myelomonocytic leukemia OTC-4 cells. Immunol Lett. 2005;99(1):130–5.PubMedCrossRef
108.
Zurück zum Zitat Nagayama H, Sato K, Kawasaki H, Enomoto M, Morimoto C, Tadokoro K, Juji T, Asano S, Takahashi TA. IL-12 responsiveness and expression of IL-12 receptor in human peripheral blood monocyte-derived dendritic cells. J Immunol. 2000;165(1):59–66.PubMed Nagayama H, Sato K, Kawasaki H, Enomoto M, Morimoto C, Tadokoro K, Juji T, Asano S, Takahashi TA. IL-12 responsiveness and expression of IL-12 receptor in human peripheral blood monocyte-derived dendritic cells. J Immunol. 2000;165(1):59–66.PubMed
109.
Zurück zum Zitat Koski GK, Lyakh LA, Cohen PA, Rice NR. CD14+ monocytes as dendritic cell precursors: diverse maturation-inducing pathways lead to common activation of NF-kappab/RelB. Crit Rev Immunol. 2001;21(1–3):179–89.PubMed Koski GK, Lyakh LA, Cohen PA, Rice NR. CD14+ monocytes as dendritic cell precursors: diverse maturation-inducing pathways lead to common activation of NF-kappab/RelB. Crit Rev Immunol. 2001;21(1–3):179–89.PubMed
110.
Zurück zum Zitat Stepnik M, Arkusz J. Molecular events associated with dendritic cells activation by contact sensitizers. Int J Occup Med Environ Health. 2003;16(3):191–9.PubMed Stepnik M, Arkusz J. Molecular events associated with dendritic cells activation by contact sensitizers. Int J Occup Med Environ Health. 2003;16(3):191–9.PubMed
111.
Zurück zum Zitat Rehani K, Wang H, Garcia CA, Kinane DF, Martin M. Toll-like receptor-mediated production of IL-1Ra is negatively regulated by GSK3 via the MAPK ERK1/2. J Immunol. 2009;182(1):547–53.PubMed Rehani K, Wang H, Garcia CA, Kinane DF, Martin M. Toll-like receptor-mediated production of IL-1Ra is negatively regulated by GSK3 via the MAPK ERK1/2. J Immunol. 2009;182(1):547–53.PubMed
112.
Zurück zum Zitat Hu X, Paik PK, Chen J, Yarilina A, Kockeritz L, Lu TT, Woodgett JR, Ivashkiv LB. IFN-gamma suppresses IL-10 production and synergizes with TLR2 by regulating GSK3 and CREB/AP-1 proteins. Immunity. 2006;24(5):563–74.PubMedCrossRef Hu X, Paik PK, Chen J, Yarilina A, Kockeritz L, Lu TT, Woodgett JR, Ivashkiv LB. IFN-gamma suppresses IL-10 production and synergizes with TLR2 by regulating GSK3 and CREB/AP-1 proteins. Immunity. 2006;24(5):563–74.PubMedCrossRef
113.
Zurück zum Zitat Spinnler K, Mezger M, Steffens M, Sennefelder H, Kurzai O, Einsele H, Loeffler J. Role of glycogen synthase kinase 3 (GSK-3) in innate immune response of human immature dendritic cells to Aspergillus fumigatus. Med Mycol. 2010;48(4):589–97.PubMedCrossRef Spinnler K, Mezger M, Steffens M, Sennefelder H, Kurzai O, Einsele H, Loeffler J. Role of glycogen synthase kinase 3 (GSK-3) in innate immune response of human immature dendritic cells to Aspergillus fumigatus. Med Mycol. 2010;48(4):589–97.PubMedCrossRef
114.
Zurück zum Zitat Lin CF, Tsai CC, Huang WC, Wang CY, Tseng HC, Wang Y, Kai JI, Wang SW, Cheng YL. IFN-gamma synergizes with LPS to induce nitric oxide biosynthesis through glycogen synthase kinase-3-inhibited IL-10. J Cell Biochem. 2008;105(3):746–55.PubMedCrossRef Lin CF, Tsai CC, Huang WC, Wang CY, Tseng HC, Wang Y, Kai JI, Wang SW, Cheng YL. IFN-gamma synergizes with LPS to induce nitric oxide biosynthesis through glycogen synthase kinase-3-inhibited IL-10. J Cell Biochem. 2008;105(3):746–55.PubMedCrossRef
115.
Zurück zum Zitat Rodionova E, Conzelmann M, Maraskovsky E, Hess M, Kirsch M, Giese T, Ho AD, Zoller M, Dreger P, Luft T. GSK-3 mediates differentiation and activation of proinflammatory dendritic cells. Blood. 2007;109(4):1584–92.PubMedCrossRef Rodionova E, Conzelmann M, Maraskovsky E, Hess M, Kirsch M, Giese T, Ho AD, Zoller M, Dreger P, Luft T. GSK-3 mediates differentiation and activation of proinflammatory dendritic cells. Blood. 2007;109(4):1584–92.PubMedCrossRef
116.
Zurück zum Zitat Duperrier K, Velten FW, Bohlender J, Demory A, Metharom P, Goerdt S. Immunosuppressive agents mediate reduced allostimulatory properties of myeloid-derived dendritic cells despite induction of divergent molecular phenotypes. Mol Immunol. 2005;42(12):1531–40.PubMedCrossRef Duperrier K, Velten FW, Bohlender J, Demory A, Metharom P, Goerdt S. Immunosuppressive agents mediate reduced allostimulatory properties of myeloid-derived dendritic cells despite induction of divergent molecular phenotypes. Mol Immunol. 2005;42(12):1531–40.PubMedCrossRef
117.
Zurück zum Zitat Lu L, Lee WC, Takayama T, Qian S, Gambotto A, Robbins PD, Thomson AW. Genetic engineering of dendritic cells to express immunosuppressive molecules (viral IL-10, TGF-beta, and CTLA4Ig). J Leukoc Biol. 1999;66(2):293–6.PubMed Lu L, Lee WC, Takayama T, Qian S, Gambotto A, Robbins PD, Thomson AW. Genetic engineering of dendritic cells to express immunosuppressive molecules (viral IL-10, TGF-beta, and CTLA4Ig). J Leukoc Biol. 1999;66(2):293–6.PubMed
118.
Zurück zum Zitat Wada A. GSK-3 inhibitors and insulin receptor signaling in health, disease, and therapeutics. Front Biosci. 2009;14:1558–70.PubMedCrossRef Wada A. GSK-3 inhibitors and insulin receptor signaling in health, disease, and therapeutics. Front Biosci. 2009;14:1558–70.PubMedCrossRef
119.
Zurück zum Zitat MacAulay K, Woodgett JR. Targeting glycogen synthase kinase-3 (GSK-3) in the treatment of Type 2 diabetes. Expert Opin Ther Targets. 2008;12(10):1265–74.PubMedCrossRef MacAulay K, Woodgett JR. Targeting glycogen synthase kinase-3 (GSK-3) in the treatment of Type 2 diabetes. Expert Opin Ther Targets. 2008;12(10):1265–74.PubMedCrossRef
120.
Zurück zum Zitat Mucci I, Legitimo A, Compagnino M, Consolini R, Migliaccio P, Metelli MR, Scatena F. The methodological approach for the generation of human dendritic cells from monocytes affects the maturation state of the resultant dendritic cells. Biologicals. 2009;37(5):288–96.PubMedCrossRef Mucci I, Legitimo A, Compagnino M, Consolini R, Migliaccio P, Metelli MR, Scatena F. The methodological approach for the generation of human dendritic cells from monocytes affects the maturation state of the resultant dendritic cells. Biologicals. 2009;37(5):288–96.PubMedCrossRef
121.
Zurück zum Zitat Elkord E, Williams PE, Kynaston H, Rowbottom AW. Human monocyte isolation methods influence cytokine production from in vitro generated dendritic cells. Immunology. 2005;114(2):204–12.PubMedCrossRef Elkord E, Williams PE, Kynaston H, Rowbottom AW. Human monocyte isolation methods influence cytokine production from in vitro generated dendritic cells. Immunology. 2005;114(2):204–12.PubMedCrossRef
122.
Zurück zum Zitat Colic M, Mojsilovic S, Pavlovic B, Vucicevic D, Majstorovic I, Bufan B, Stojic-Vukanic Z, Vasilijic S, Vucevic D, Gasic S, et al. Comparison of two different protocols for the induction of maturation of human dendritic cells in vitro. Vojnosanit Pregl. 2004;61(5):471–8.PubMedCrossRef Colic M, Mojsilovic S, Pavlovic B, Vucicevic D, Majstorovic I, Bufan B, Stojic-Vukanic Z, Vasilijic S, Vucevic D, Gasic S, et al. Comparison of two different protocols for the induction of maturation of human dendritic cells in vitro. Vojnosanit Pregl. 2004;61(5):471–8.PubMedCrossRef
123.
124.
Zurück zum Zitat Franke TF, Hornik CP, Segev L, Shostak GA, Sugimoto C. PI3K/Akt and apoptosis: size matters. Oncogene. 2003;22(56):8983–98.PubMedCrossRef Franke TF, Hornik CP, Segev L, Shostak GA, Sugimoto C. PI3K/Akt and apoptosis: size matters. Oncogene. 2003;22(56):8983–98.PubMedCrossRef
125.
Zurück zum Zitat McCubrey JA, Steelman LS, Abrams SL, Bertrand FE, Ludwig DE, Basecke J, Libra M, Stivala F, Milella M, Tafuri A, et al. Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy. Leukemia. 2008;22(4):708–22.PubMedCrossRef McCubrey JA, Steelman LS, Abrams SL, Bertrand FE, Ludwig DE, Basecke J, Libra M, Stivala F, Milella M, Tafuri A, et al. Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy. Leukemia. 2008;22(4):708–22.PubMedCrossRef
126.
Zurück zum Zitat Cho DC, Cohen MB, Panka DJ, Collins M, Ghebremichael M, Atkins MB, Signoretti S, Mier JW. The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma. Clin Cancer Res. 2010;16(14):3628–38.PubMedCrossRef Cho DC, Cohen MB, Panka DJ, Collins M, Ghebremichael M, Atkins MB, Signoretti S, Mier JW. The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma. Clin Cancer Res. 2010;16(14):3628–38.PubMedCrossRef
127.
Zurück zum Zitat Fujiwara M, Izuishi K, Sano T, Hossain MA, Kimura S, Masaki T, Suzuki Y. Modulating effect of the PI3-kinase inhibitor LY294002 on cisplatin in human pancreatic cancer cells. J Exp Clin Cancer Res. 2008;27:76.PubMedCrossRef Fujiwara M, Izuishi K, Sano T, Hossain MA, Kimura S, Masaki T, Suzuki Y. Modulating effect of the PI3-kinase inhibitor LY294002 on cisplatin in human pancreatic cancer cells. J Exp Clin Cancer Res. 2008;27:76.PubMedCrossRef
128.
Zurück zum Zitat Burchert A, Wang Y, Cai D, von Bubnoff N, Paschka P, Muller-Brusselbach S, Ottmann OG, Duyster J, Hochhaus A, Neubauer A. Compensatory PI3-kinase/Akt/mTor activation regulates imatinib resistance development. Leukemia. 2005;19(10):1774–82.PubMedCrossRef Burchert A, Wang Y, Cai D, von Bubnoff N, Paschka P, Muller-Brusselbach S, Ottmann OG, Duyster J, Hochhaus A, Neubauer A. Compensatory PI3-kinase/Akt/mTor activation regulates imatinib resistance development. Leukemia. 2005;19(10):1774–82.PubMedCrossRef
129.
Zurück zum Zitat Aikawa R, Nawano M, Gu Y, Katagiri H, Asano T, Zhu W, Nagai R, Komuro I. Insulin prevents cardiomyocytes from oxidative stress-induced apoptosis through activation of PI3 kinase/Akt. Circulation. 2000;102(23):2873–9.PubMed Aikawa R, Nawano M, Gu Y, Katagiri H, Asano T, Zhu W, Nagai R, Komuro I. Insulin prevents cardiomyocytes from oxidative stress-induced apoptosis through activation of PI3 kinase/Akt. Circulation. 2000;102(23):2873–9.PubMed
130.
Zurück zum Zitat Rane MJ, Coxon PY, Powell DW, Webster R, Klein JB, Pierce W, Ping P, McLeish KR. p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils. J Biol Chem. 2001;276(5):3517–23.PubMedCrossRef Rane MJ, Coxon PY, Powell DW, Webster R, Klein JB, Pierce W, Ping P, McLeish KR. p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils. J Biol Chem. 2001;276(5):3517–23.PubMedCrossRef
131.
Zurück zum Zitat Berra E, Diaz-Meco MT, Moscat J. The activation of p38 and apoptosis by the inhibition of Erk is antagonized by the phosphoinositide 3-kinase/Akt pathway. J Biol Chem. 1998;273(17):10792–7.PubMedCrossRef Berra E, Diaz-Meco MT, Moscat J. The activation of p38 and apoptosis by the inhibition of Erk is antagonized by the phosphoinositide 3-kinase/Akt pathway. J Biol Chem. 1998;273(17):10792–7.PubMedCrossRef
132.
Zurück zum Zitat Gratton JP, Morales-Ruiz M, Kureishi Y, Fulton D, Walsh K, Sessa WC. Akt down-regulation of p38 signaling provides a novel mechanism of vascular endothelial growth factor-mediated cytoprotection in endothelial cells. J Biol Chem. 2001;276(32):30359–65.PubMedCrossRef Gratton JP, Morales-Ruiz M, Kureishi Y, Fulton D, Walsh K, Sessa WC. Akt down-regulation of p38 signaling provides a novel mechanism of vascular endothelial growth factor-mediated cytoprotection in endothelial cells. J Biol Chem. 2001;276(32):30359–65.PubMedCrossRef
133.
Zurück zum Zitat Ammon C, Mondal K, Andreesen R, Krause SW. Differential expression of the transcription factor NF-kappaB during human mononuclear phagocyte differentiation to macrophages and dendritic cells. Biochem Biophys Res Commun. 2000;268(1):99–105.PubMedCrossRef Ammon C, Mondal K, Andreesen R, Krause SW. Differential expression of the transcription factor NF-kappaB during human mononuclear phagocyte differentiation to macrophages and dendritic cells. Biochem Biophys Res Commun. 2000;268(1):99–105.PubMedCrossRef
134.
Zurück zum Zitat Rescigno M, Martino M, Sutherland CL, Gold MR, Ricciardi-Castagnoli P. Dendritic cell survival and maturation are regulated by different signaling pathways. J Exp Med. 1998;188(11):2175–80.PubMedCrossRef Rescigno M, Martino M, Sutherland CL, Gold MR, Ricciardi-Castagnoli P. Dendritic cell survival and maturation are regulated by different signaling pathways. J Exp Med. 1998;188(11):2175–80.PubMedCrossRef
135.
Zurück zum Zitat Jones RG, Saibil SD, Pun JM, Elford AR, Bonnard M, Pellegrini M, Arya S, Parsons ME, Krawczyk CM, Gerondakis S, et al. NF-kappaB couples protein kinase B/Akt signaling to distinct survival pathways and the regulation of lymphocyte homeostasis in vivo. J Immunol. 2005;175(6):3790–9.PubMed Jones RG, Saibil SD, Pun JM, Elford AR, Bonnard M, Pellegrini M, Arya S, Parsons ME, Krawczyk CM, Gerondakis S, et al. NF-kappaB couples protein kinase B/Akt signaling to distinct survival pathways and the regulation of lymphocyte homeostasis in vivo. J Immunol. 2005;175(6):3790–9.PubMed
136.
Zurück zum Zitat Ohashi PS, Woodgett JR. Modulating autoimmunity: pick your PI3 kinase. Nat Med. 2005;11(9):924–5.PubMedCrossRef Ohashi PS, Woodgett JR. Modulating autoimmunity: pick your PI3 kinase. Nat Med. 2005;11(9):924–5.PubMedCrossRef
137.
Zurück zum Zitat Woodgett JR, Ohashi PS. GSK3: an in-toll-erant protein kinase? Nat Immunol. 2005;6(8):751–2.PubMedCrossRef Woodgett JR, Ohashi PS. GSK3: an in-toll-erant protein kinase? Nat Immunol. 2005;6(8):751–2.PubMedCrossRef
138.
Zurück zum Zitat Dil N, Marshall AJ. Role of phosphoinositide 3-kinase p110 delta in TLR4- and TLR9-mediated B cell cytokine production and differentiation. Mol Immunol. 2009;46(10):1970–8.PubMedCrossRef Dil N, Marshall AJ. Role of phosphoinositide 3-kinase p110 delta in TLR4- and TLR9-mediated B cell cytokine production and differentiation. Mol Immunol. 2009;46(10):1970–8.PubMedCrossRef
139.
Zurück zum Zitat Hoarau C, Gerard B, Lescanne E, Henry D, Francois S, Lacapere JJ, El Benna J, Dang PM, Grandchamp B, Lebranchu Y, et al. TLR9 activation induces normal neutrophil responses in a child with IRAK-4 deficiency: involvement of the direct PI3K pathway. J Immunol. 2007;179(7):4754–65.PubMed Hoarau C, Gerard B, Lescanne E, Henry D, Francois S, Lacapere JJ, El Benna J, Dang PM, Grandchamp B, Lebranchu Y, et al. TLR9 activation induces normal neutrophil responses in a child with IRAK-4 deficiency: involvement of the direct PI3K pathway. J Immunol. 2007;179(7):4754–65.PubMed
140.
Zurück zum Zitat Sester DP, Brion K, Trieu A, Goodridge HS, Roberts TL, Dunn J, Hume DA, Stacey KJ, Sweet MJ. CpG DNA activates survival in murine macrophages through TLR9 and the phosphatidylinositol 3-kinase-Akt pathway. J Immunol. 2006;177(7):4473–80.PubMed Sester DP, Brion K, Trieu A, Goodridge HS, Roberts TL, Dunn J, Hume DA, Stacey KJ, Sweet MJ. CpG DNA activates survival in murine macrophages through TLR9 and the phosphatidylinositol 3-kinase-Akt pathway. J Immunol. 2006;177(7):4473–80.PubMed
Metadaten
Titel
Phosphatidylinositol-3-kinase activity during in vitro dendritic cell generation determines suppressive or stimulatory capacity
verfasst von
Valentina Di Caro
Antonella D’Anneo
Brett Phillips
Carl Engman
Jo Harnaha
Massimo Trucco
Nick Giannoukakis
Publikationsdatum
01.08.2011
Verlag
Humana Press Inc
Erschienen in
Immunologic Research / Ausgabe 2-3/2011
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI
https://doi.org/10.1007/s12026-011-8206-1

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