Skip to main content
Erschienen in: Annals of Hematology 3/2012

01.03.2012 | Original Article

Tcf-1 gene silence suppresses downstream gene expression in CD4+ T cells from bone marrow of aplastic anemia patients

verfasst von: Miao Zheng, Kai Zheng, Jianfeng Zhou, Hanying Sun, Lifang Huang, Wenli Liu

Erschienen in: Annals of Hematology | Ausgabe 3/2012

Einloggen, um Zugang zu erhalten

Abstract

CD4+ T cells play a crucial role in the pathogenesis of acquired aplastic anemia (AA). Tcf-1 gene regulates T cell development and function, and it is significantly upregulated in the bone marrow CD4+ T cells from patients with acquired AA. To explore the role of Tcf-1 in the pathogenesis of AA, we knocked down Tcf-1 gene in CD4+ T cells of AA patients and studied the effects of Tcf-1 silencing on its downstream gene expression. Upon transfection of psiRNA into marrow CD4+ T cells from bone marrow of aplastic anemia patients, the expression of Tcf-1 was significantly knocked down; consequently, expressions of c-Myc and CD44 were also significantly reduced. Our results suggest that Tcf-1 may contribute to pathogenesis of AA by regulating downstream gene expression such as c-myc and CD44.
Literatur
1.
Zurück zum Zitat Nakao S, Takami A, Takamatsu H, Zeng W, Sugimori N, Yamazaki H, Miura Y, Ueda M, Shiobara S, Yoshioka T, Kaneshige T, Yasukawa M, Matsuda T (1997) Isolation of a T-cell clone showing HLA-DRB1*0405-restricted cytotoxicity for hematopoietic cells in a patient with aplastic anemia. Blood 89:3691–3699PubMed Nakao S, Takami A, Takamatsu H, Zeng W, Sugimori N, Yamazaki H, Miura Y, Ueda M, Shiobara S, Yoshioka T, Kaneshige T, Yasukawa M, Matsuda T (1997) Isolation of a T-cell clone showing HLA-DRB1*0405-restricted cytotoxicity for hematopoietic cells in a patient with aplastic anemia. Blood 89:3691–3699PubMed
2.
Zurück zum Zitat Zheng M, Liu W, Fu JR, Sun H, Zhou JF, Hui-zhen XU (2007) Screening of aplastic anaemia-related genes in bone marrow CD4+ T cells by suppressive subtractive hybridization. Chin Med J 120:1326–1330PubMed Zheng M, Liu W, Fu JR, Sun H, Zhou JF, Hui-zhen XU (2007) Screening of aplastic anaemia-related genes in bone marrow CD4+ T cells by suppressive subtractive hybridization. Chin Med J 120:1326–1330PubMed
3.
Zurück zum Zitat Zeng W, Kajigaya S, Chen G, Risitano AM, Nunez O, Young NS (2004) Transcript profile of CD4+ and CD8+ T cells from the bone marrow of acquired aplastic anemia patients. Exp Hematol 32:806–814PubMedCrossRef Zeng W, Kajigaya S, Chen G, Risitano AM, Nunez O, Young NS (2004) Transcript profile of CD4+ and CD8+ T cells from the bone marrow of acquired aplastic anemia patients. Exp Hematol 32:806–814PubMedCrossRef
4.
Zurück zum Zitat Pongracz J, Hare K, Harman B, Anderson G, Jenkinson EJ (2003) Thymic epithelial cells provide Wnt signals to developing thymocytes. Eur J Immunity 33:1949–1956CrossRef Pongracz J, Hare K, Harman B, Anderson G, Jenkinson EJ (2003) Thymic epithelial cells provide Wnt signals to developing thymocytes. Eur J Immunity 33:1949–1956CrossRef
5.
Zurück zum Zitat Schilham MW, Wilsom A, Moerer P, Benaissa-Trouw BJ, Cumano A, Clevers HC (1998) Critical involvement of Tcf-1 in expansion of thymocytes. J Immunol 161:3984–3991PubMed Schilham MW, Wilsom A, Moerer P, Benaissa-Trouw BJ, Cumano A, Clevers HC (1998) Critical involvement of Tcf-1 in expansion of thymocytes. J Immunol 161:3984–3991PubMed
6.
Zurück zum Zitat Ioannidis V, Beermann F, Clevers H, Held W (2001) The β-catenin TCF-1 pathway ensures CD4+CD8+ thymocyte survival. Nat Immunol 2:691–697PubMedCrossRef Ioannidis V, Beermann F, Clevers H, Held W (2001) The β-catenin TCF-1 pathway ensures CD4+CD8+ thymocyte survival. Nat Immunol 2:691–697PubMedCrossRef
7.
Zurück zum Zitat Staal FJ, Meeldijk J, Moerer P, Jay P, van de Weerdt BC, Vainio S, Nolan GP, Clevers H (2001) Wnt signaling is required for thymocyte development and activates Tcf-1 mediated transcription. Eur J Immunol 31:285–293PubMedCrossRef Staal FJ, Meeldijk J, Moerer P, Jay P, van de Weerdt BC, Vainio S, Nolan GP, Clevers H (2001) Wnt signaling is required for thymocyte development and activates Tcf-1 mediated transcription. Eur J Immunol 31:285–293PubMedCrossRef
8.
Zurück zum Zitat Yu Q, Sharma A, Sen JM (2010) TCF1 and beta-catenin regulate T cell development and function. Immunol Res 47:45–55PubMedCrossRef Yu Q, Sharma A, Sen JM (2010) TCF1 and beta-catenin regulate T cell development and function. Immunol Res 47:45–55PubMedCrossRef
9.
Zurück zum Zitat Nácher M, Blázquez AB, Shao B, Matesanz A, Prophete C, Berin MC, Frenette PS, Hidalgo A (2011) Physiological contribution of CD44 as a ligand for E-selectin during inflammatory T-cell recruitment. Am J Pathol 178:2437–2446PubMedCrossRef Nácher M, Blázquez AB, Shao B, Matesanz A, Prophete C, Berin MC, Frenette PS, Hidalgo A (2011) Physiological contribution of CD44 as a ligand for E-selectin during inflammatory T-cell recruitment. Am J Pathol 178:2437–2446PubMedCrossRef
10.
Zurück zum Zitat Baaten BJ, Li CR, Bradley LM (2010) Multifaceted regulation of T cells by CD44. Commun Integr Biol 3:508–512PubMedCrossRef Baaten BJ, Li CR, Bradley LM (2010) Multifaceted regulation of T cells by CD44. Commun Integr Biol 3:508–512PubMedCrossRef
11.
Zurück zum Zitat Young NS, Calado RT, Scheinberg P (2006) Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 108:2509–2519PubMedCrossRef Young NS, Calado RT, Scheinberg P (2006) Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 108:2509–2519PubMedCrossRef
12.
Zurück zum Zitat Risitano AM (2011) Immunosuppressive therapies in the management of immune-mediated marrow failures in adults: where we stand and where we are going. Br J Haematol 152:127–140PubMedCrossRef Risitano AM (2011) Immunosuppressive therapies in the management of immune-mediated marrow failures in adults: where we stand and where we are going. Br J Haematol 152:127–140PubMedCrossRef
13.
Zurück zum Zitat Passweg JR, Marsh JC (2010) Aplastic anemia: first-line treatment by immunosuppression and sibling marrow transplantation. Hematology Am Soc Hematol Educ Program 2010:36–42PubMedCrossRef Passweg JR, Marsh JC (2010) Aplastic anemia: first-line treatment by immunosuppression and sibling marrow transplantation. Hematology Am Soc Hematol Educ Program 2010:36–42PubMedCrossRef
14.
Zurück zum Zitat Giannakoulas NC, Karakantza M, Theodorou GL, Pagoni M, Galanopoulos A, Kakagianni T, Kouraklis-Symeonidis A, Matsouka P, Maniatis A, Zoumbos NC (2004) Clinical relevance of balance between type 1 and type 2 immune responses of lymphocyte subpopulations in aplastic anaemia patients. Br J Haematol 124:97–105PubMedCrossRef Giannakoulas NC, Karakantza M, Theodorou GL, Pagoni M, Galanopoulos A, Kakagianni T, Kouraklis-Symeonidis A, Matsouka P, Maniatis A, Zoumbos NC (2004) Clinical relevance of balance between type 1 and type 2 immune responses of lymphocyte subpopulations in aplastic anaemia patients. Br J Haematol 124:97–105PubMedCrossRef
15.
Zurück zum Zitat He H, Shao Z, He G, Liu H, Shi J, Fu R, Zhao M, Bai J, Jia H, Sun J, Cui Z, Chu Y, Yang T, Yang C (2002) Role of Th1 cell in the pathogenesis of aplastic anemia. Chin J Hematol 23:574–577 He H, Shao Z, He G, Liu H, Shi J, Fu R, Zhao M, Bai J, Jia H, Sun J, Cui Z, Chu Y, Yang T, Yang C (2002) Role of Th1 cell in the pathogenesis of aplastic anemia. Chin J Hematol 23:574–577
16.
Zurück zum Zitat Hu X, Gu Y, Wang Y, Cong Y, Qu X, Xu C (2009) Increased CD4+ and CD8+ effector memory T cells in patients with aplastic anemia. Haematologica 94:428–429PubMedCrossRef Hu X, Gu Y, Wang Y, Cong Y, Qu X, Xu C (2009) Increased CD4+ and CD8+ effector memory T cells in patients with aplastic anemia. Haematologica 94:428–429PubMedCrossRef
17.
Zurück zum Zitat Maciejewski JP, Risitano A, Kook H, Zeng W, Chen G, Young NS (2002) Immune pathophysiology of aplastic anemia. Int J Hematol 76:207–214PubMedCrossRef Maciejewski JP, Risitano A, Kook H, Zeng W, Chen G, Young NS (2002) Immune pathophysiology of aplastic anemia. Int J Hematol 76:207–214PubMedCrossRef
18.
Zurück zum Zitat Zheng M, Sun H, Zhou J, Xu H, Huang L, Liu W (2010) Proliferation and apoptosis of bone marrow CD4+ T cells in patients with aplastic anemia and impacts of the secreted cytokines on hematopoietic stem cells from umbilical cord blood. J Huazhong Univ Sci Technolog Med Sci 30:37–41PubMedCrossRef Zheng M, Sun H, Zhou J, Xu H, Huang L, Liu W (2010) Proliferation and apoptosis of bone marrow CD4+ T cells in patients with aplastic anemia and impacts of the secreted cytokines on hematopoietic stem cells from umbilical cord blood. J Huazhong Univ Sci Technolog Med Sci 30:37–41PubMedCrossRef
19.
Zurück zum Zitat Jim B, Antohio MH (1983) The human c-myc oncogene: structural consequences of translocation into the IgH locus in Burkitt lymphoma. Cell 34:779–787CrossRef Jim B, Antohio MH (1983) The human c-myc oncogene: structural consequences of translocation into the IgH locus in Burkitt lymphoma. Cell 34:779–787CrossRef
20.
Zurück zum Zitat Kelly K, Cochran BH, Stiles CD, Leder P (1983) Cell-specific regulation of the c-Myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell 35:603–610PubMedCrossRef Kelly K, Cochran BH, Stiles CD, Leder P (1983) Cell-specific regulation of the c-Myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell 35:603–610PubMedCrossRef
21.
Zurück zum Zitat Tolg C, Hofmann M, Herrlieh P, Ponta H (1993) Splicing choice from ten variant exon establishes CD44 variability. Nucleic Acids Res 21:1225–1229PubMedCrossRef Tolg C, Hofmann M, Herrlieh P, Ponta H (1993) Splicing choice from ten variant exon establishes CD44 variability. Nucleic Acids Res 21:1225–1229PubMedCrossRef
22.
Zurück zum Zitat Osada A, Nakashima H, Furue M, Tamaki K (1995) Up-regulation of CD44 expression by tumor necrosis factor-alpha is neutralized by interleukin-10 in Langerhans cells. J Invest Dermatol 105:124–127PubMedCrossRef Osada A, Nakashima H, Furue M, Tamaki K (1995) Up-regulation of CD44 expression by tumor necrosis factor-alpha is neutralized by interleukin-10 in Langerhans cells. J Invest Dermatol 105:124–127PubMedCrossRef
23.
Zurück zum Zitat Oppenheimer-Marks N, Davis LS, Lipsky PE (1990) Human T lymphocyte adhesion to endothelial cell and transendothelinl migration: alteration of receptor use relates to the activation status of both the T cell and endothelial cell. J Immunol 145:140–148PubMed Oppenheimer-Marks N, Davis LS, Lipsky PE (1990) Human T lymphocyte adhesion to endothelial cell and transendothelinl migration: alteration of receptor use relates to the activation status of both the T cell and endothelial cell. J Immunol 145:140–148PubMed
24.
Zurück zum Zitat Baum HP, Schimd T, Schock G, Reichrath J (1996) Expression of CD44 isoforms in basal cell carcinomas. Br J Dermatol 134:465–478PubMedCrossRef Baum HP, Schimd T, Schock G, Reichrath J (1996) Expression of CD44 isoforms in basal cell carcinomas. Br J Dermatol 134:465–478PubMedCrossRef
Metadaten
Titel
Tcf-1 gene silence suppresses downstream gene expression in CD4+ T cells from bone marrow of aplastic anemia patients
verfasst von
Miao Zheng
Kai Zheng
Jianfeng Zhou
Hanying Sun
Lifang Huang
Wenli Liu
Publikationsdatum
01.03.2012
Verlag
Springer-Verlag
Erschienen in
Annals of Hematology / Ausgabe 3/2012
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-011-1314-0

Weitere Artikel der Ausgabe 3/2012

Annals of Hematology 3/2012 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.