Skip to main content
Erschienen in: Endocrine 1/2022

24.01.2022 | Original Article

Anti-CD20 therapy ameliorates β cell function and rebalances Th17/Treg cells in NOD mice

verfasst von: Min Chen, Qianhui Zhang, Yanhong Wei, Qianqian Wan, Min Xu, Xiaoqi Chen

Erschienen in: Endocrine | Ausgabe 1/2022

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Anti-CD20 therapy delays type 1 diabetes mellitus (T1DM) progression in both nonobese diabetic (NOD) mice and new-onset patients. The mechanism is not completely defined. This study aimed to investigate the effects of anti-CD20 therapy on T helper 17 (Th17) cells and regulatory T cells (Tregs) in NOD mice. The role of B cell depletion in T1DM development was also examined.

Methods

NOD mice were randomly divided into two groups. The mice in the experimental group were treated with an anti-CD20 antibody, while the control mice were treated with an isotype-matched control antibody. After treatment, islet morphology and inflammation, Th17 and Treg cell frequencies in the pancreas and spleen, serum cytokine and anti-glutamic acid decarboxylase (GAD) antibody levels, interleukin (IL)-17A levels in the pancreas and spleen, insulin expression in islet cells and islet β cell function were measured.

Results

Decreased blood glucose and increased insulin secretion were found in the exprimental group compared with the CON group. A lower islet inflammation score was also found in the experimental group. Decreased Th17 cell and IL-17A levels and augmented Treg cell levels were found in the spleen and pancreas after anti-CD20 treatment. The serum levels of B cell activating factor (BAFF), IL-17A, IL-17F, IL-23 and anti-GAD autoantibodies were decreased in the experimental group, while higher serum levels of IL-10 and transforming growth factor (TGF)-β were found.

Conclusion

Anti-CD20 therapy might have some beneficial effects that improve β cell function by relieving islet inflammation through regulation of Th17/Treg cells and the proinflammatory/anti-inflammatory balance.
Literatur
1.
Zurück zum Zitat K.C. Herold, D.A. Vignali, A. Cooke, J.A. Bluestone, Type 1 diabetes: translating mechanistic observations into effective clinical outcomes. Nat. Rev. Immunol. 13, 243–256 (2013)CrossRef K.C. Herold, D.A. Vignali, A. Cooke, J.A. Bluestone, Type 1 diabetes: translating mechanistic observations into effective clinical outcomes. Nat. Rev. Immunol. 13, 243–256 (2013)CrossRef
2.
Zurück zum Zitat J.M. Norris, R.K. Johnson, L.C. Stene, Type 1 diabetes-early life origins and changing epidemiology. lancet Diabetes Endocrinol. 8, 226–238 (2020)CrossRef J.M. Norris, R.K. Johnson, L.C. Stene, Type 1 diabetes-early life origins and changing epidemiology. lancet Diabetes Endocrinol. 8, 226–238 (2020)CrossRef
3.
Zurück zum Zitat M.S. Anderson, J.A. Bluestone, The NOD mouse: a model of immune dysregulation. Annu. Rev. Immunol. 23, 447–485 (2005)CrossRef M.S. Anderson, J.A. Bluestone, The NOD mouse: a model of immune dysregulation. Annu. Rev. Immunol. 23, 447–485 (2005)CrossRef
4.
Zurück zum Zitat M. Pawlak, A.W. Ho, V.K. Kuchroo, Cytokines and transcription factors in the differentiation of CD4(+) T helper cell subsets and induction of tissue inflammation and autoimmunity. Curr. Opin. Immunol. 67, 57–67 (2020)CrossRef M. Pawlak, A.W. Ho, V.K. Kuchroo, Cytokines and transcription factors in the differentiation of CD4(+) T helper cell subsets and induction of tissue inflammation and autoimmunity. Curr. Opin. Immunol. 67, 57–67 (2020)CrossRef
5.
Zurück zum Zitat A. Abdel-Moneim, H.H. Bakery, G. Allam, The potential pathogenic role of IL-17/Th17 cells in both type 1 and type 2 diabetes mellitus. Biomedicine Pharmacother. = Biomedecine pharmacotherapie 101, 287–292 (2018)CrossRef A. Abdel-Moneim, H.H. Bakery, G. Allam, The potential pathogenic role of IL-17/Th17 cells in both type 1 and type 2 diabetes mellitus. Biomedicine Pharmacother. = Biomedecine pharmacotherapie 101, 287–292 (2018)CrossRef
6.
Zurück zum Zitat S.M. Cabrera, M.R. Rigby, R.G. Mirmira, Targeting regulatory T cells in the treatment of type 1 diabetes mellitus. Curr. Mol. Med. 12, 1261–1272 (2012)CrossRef S.M. Cabrera, M.R. Rigby, R.G. Mirmira, Targeting regulatory T cells in the treatment of type 1 diabetes mellitus. Curr. Mol. Med. 12, 1261–1272 (2012)CrossRef
7.
Zurück zum Zitat M. Ryba-Stanisławowska, M. Skrzypkowska, J. Myśliwska, M. Myśliwiec, The serum IL-6 profile and Treg/Th17 peripheral cell populations in patients with type 1 diabetes. Mediators Inflamm. 2013, 205284 (2013)CrossRef M. Ryba-Stanisławowska, M. Skrzypkowska, J. Myśliwska, M. Myśliwiec, The serum IL-6 profile and Treg/Th17 peripheral cell populations in patients with type 1 diabetes. Mediators Inflamm. 2013, 205284 (2013)CrossRef
8.
Zurück zum Zitat A. Ferraro, C. Socci, A. Stabilini, A. Valle, P. Monti, L. Piemonti, R. Nano, S. Olek, P. Maffi, M. Scavini, A. Secchi, C. Staudacher, E. Bonifacio, M. Battaglia, Expansion of Th17 cells and functional defects in T regulatory cells are key features of the pancreatic lymph nodes in patients with type 1 diabetes. Diabetes 60, 2903–2913 (2011)CrossRef A. Ferraro, C. Socci, A. Stabilini, A. Valle, P. Monti, L. Piemonti, R. Nano, S. Olek, P. Maffi, M. Scavini, A. Secchi, C. Staudacher, E. Bonifacio, M. Battaglia, Expansion of Th17 cells and functional defects in T regulatory cells are key features of the pancreatic lymph nodes in patients with type 1 diabetes. Diabetes 60, 2903–2913 (2011)CrossRef
9.
Zurück zum Zitat S.K. O’Neill, E. Liu, J.C. Cambier, Change you can B(cell)eive in: recent progress confirms a critical role for B cells in type 1 diabetes. Curr. Opin. Endocrinol. Diabetes, Obes. 16, 293–298 (2009)CrossRef S.K. O’Neill, E. Liu, J.C. Cambier, Change you can B(cell)eive in: recent progress confirms a critical role for B cells in type 1 diabetes. Curr. Opin. Endocrinol. Diabetes, Obes. 16, 293–298 (2009)CrossRef
10.
Zurück zum Zitat D.V. Serreze, H.D. Chapman, D.S. Varnum, M.S. Hanson, P.C. Reifsnyder, S.D. Richard, S.A. Fleming, E.H. Leiter, L.D. Shultz, B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new “speed congenic” stock of NOD.Ig mu null mice. J. Exp. Med. 184, 2049–2053 (1996)CrossRef D.V. Serreze, H.D. Chapman, D.S. Varnum, M.S. Hanson, P.C. Reifsnyder, S.D. Richard, S.A. Fleming, E.H. Leiter, L.D. Shultz, B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new “speed congenic” stock of NOD.Ig mu null mice. J. Exp. Med. 184, 2049–2053 (1996)CrossRef
11.
Zurück zum Zitat R.M. Hinman, M.J. Smith, J.C. Cambier, B cells and type 1 diabetes…in mice and men. Immunol. Lett. 160, 128–132 (2014)CrossRef R.M. Hinman, M.J. Smith, J.C. Cambier, B cells and type 1 diabetes…in mice and men. Immunol. Lett. 160, 128–132 (2014)CrossRef
12.
Zurück zum Zitat G. Zekavat, S.Y. Rostami, A. Badkerhanian, R.F. Parsons, B. Koeberlein, M. Yu, C.D. Ward, T.S. Migone, L. Yu, G.S. Eisenbarth, M.P. Cancro, A. Naji, H. Noorchashm, In vivo BLyS/BAFF neutralization ameliorates islet-directed autoimmunity in nonobese diabetic mice. J. Immunol. (Baltim., Md: 1950) 181, 8133–8144 (2008) G. Zekavat, S.Y. Rostami, A. Badkerhanian, R.F. Parsons, B. Koeberlein, M. Yu, C.D. Ward, T.S. Migone, L. Yu, G.S. Eisenbarth, M.P. Cancro, A. Naji, H. Noorchashm, In vivo BLyS/BAFF neutralization ameliorates islet-directed autoimmunity in nonobese diabetic mice. J. Immunol. (Baltim., Md: 1950) 181, 8133–8144 (2008)
13.
Zurück zum Zitat A. Tang, C. Li, Z. Chen, T. Li, Anti-CD20 monoclonal antibody combined with adenovirus vector-mediated IL-10 regulates spleen CD4+/CD8+ T cells and T-bet/GATA-3 expression in NOD mice. Mol. Med. Rep. 16, 3974–3982 (2017)CrossRef A. Tang, C. Li, Z. Chen, T. Li, Anti-CD20 monoclonal antibody combined with adenovirus vector-mediated IL-10 regulates spleen CD4+/CD8+ T cells and T-bet/GATA-3 expression in NOD mice. Mol. Med. Rep. 16, 3974–3982 (2017)CrossRef
14.
Zurück zum Zitat G. Pavlasova, M. Mraz, The regulation and function of CD20: an “enigma” of B-cell biology and targeted therapy. Haematologica 105, 1494–1506 (2020)CrossRef G. Pavlasova, M. Mraz, The regulation and function of CD20: an “enigma” of B-cell biology and targeted therapy. Haematologica 105, 1494–1506 (2020)CrossRef
15.
Zurück zum Zitat Y. Hamaguchi, Y. Xiu, K. Komura, F. Nimmerjahn, T.F. Tedder, Antibody isotype-specific engagement of Fcgamma receptors regulates B lymphocyte depletion during CD20 immunotherapy. J. Exp. Med. 203, 743–753 (2006)CrossRef Y. Hamaguchi, Y. Xiu, K. Komura, F. Nimmerjahn, T.F. Tedder, Antibody isotype-specific engagement of Fcgamma receptors regulates B lymphocyte depletion during CD20 immunotherapy. J. Exp. Med. 203, 743–753 (2006)CrossRef
16.
Zurück zum Zitat Y. Zhao, P. Alard, M.M. Kosiewicz, High thymic output of effector CD4(+) cells may lead to a Treg: T effector imbalance in the periphery in NOD mice. J. Immunol. Res. 2019, 8785263 (2019)PubMedPubMedCentral Y. Zhao, P. Alard, M.M. Kosiewicz, High thymic output of effector CD4(+) cells may lead to a Treg: T effector imbalance in the periphery in NOD mice. J. Immunol. Res. 2019, 8785263 (2019)PubMedPubMedCentral
17.
Zurück zum Zitat T. Hayashi, K. Yoshinaka, K. Hasegawa, K. Maeda, T. Onodera, CpG oligodeoxynucleotides accelerate reovirus type 2-triggered insulitis in DBA/1 suckling mice. Int. J. Exp. Pathol. 83, 217–223 (2002)CrossRef T. Hayashi, K. Yoshinaka, K. Hasegawa, K. Maeda, T. Onodera, CpG oligodeoxynucleotides accelerate reovirus type 2-triggered insulitis in DBA/1 suckling mice. Int. J. Exp. Pathol. 83, 217–223 (2002)CrossRef
18.
Zurück zum Zitat M. Basu, K. Pandit, M. Banerjee, S.A. Mondal, P. Mukhopadhyay, S. Ghosh, Profile of auto-antibodies (disease related and other) in children with type 1 diabetes. Indian J. Endocrinol. Metab. 24, 256–259 (2020)CrossRef M. Basu, K. Pandit, M. Banerjee, S.A. Mondal, P. Mukhopadhyay, S. Ghosh, Profile of auto-antibodies (disease related and other) in children with type 1 diabetes. Indian J. Endocrinol. Metab. 24, 256–259 (2020)CrossRef
19.
Zurück zum Zitat J. Ilonen, J. Lempainen, R. Veijola, The heterogeneous pathogenesis of type 1 diabetes mellitus. Nat. Rev. Endocrinol. 15, 635–650 (2019)CrossRef J. Ilonen, J. Lempainen, R. Veijola, The heterogeneous pathogenesis of type 1 diabetes mellitus. Nat. Rev. Endocrinol. 15, 635–650 (2019)CrossRef
20.
Zurück zum Zitat F.S. Wong, L. Wen, M. Tang, M. Ramanathan, I. Visintin, J. Daugherty, L.G. Hannum, C.A. Janeway Jr., M.J. Shlomchik, Investigation of the role of B-cells in type 1 diabetes in the NOD mouse. Diabetes 53, 2581–2587 (2004)CrossRef F.S. Wong, L. Wen, M. Tang, M. Ramanathan, I. Visintin, J. Daugherty, L.G. Hannum, C.A. Janeway Jr., M.J. Shlomchik, Investigation of the role of B-cells in type 1 diabetes in the NOD mouse. Diabetes 53, 2581–2587 (2004)CrossRef
21.
Zurück zum Zitat C.R. Smulski, H. Eibel, BAFF and BAFF-receptor in B cell selection and survival. Front. Immunol. 9, 2285 (2018)CrossRef C.R. Smulski, H. Eibel, BAFF and BAFF-receptor in B cell selection and survival. Front. Immunol. 9, 2285 (2018)CrossRef
22.
Zurück zum Zitat S. Nakayamada, Y. Tanaka, BAFF- and APRIL-targeted therapy in systemic autoimmune diseases. Inflamm. regeneration 36, 6 (2016)CrossRef S. Nakayamada, Y. Tanaka, BAFF- and APRIL-targeted therapy in systemic autoimmune diseases. Inflamm. regeneration 36, 6 (2016)CrossRef
23.
Zurück zum Zitat G.A. Lied, A. Berstad, Functional and clinical aspects of the B-cell-activating factor (BAFF): a narrative review. Scand. J. Immunol. 73, 1–7 (2011)CrossRef G.A. Lied, A. Berstad, Functional and clinical aspects of the B-cell-activating factor (BAFF): a narrative review. Scand. J. Immunol. 73, 1–7 (2011)CrossRef
24.
Zurück zum Zitat Y. Xiu, C.P. Wong, J.D. Bouaziz, Y. Hamaguchi, Y. Wang, S.M. Pop, R.M. Tisch, T.F. Tedder, B lymphocyte depletion by CD20 monoclonal antibody prevents diabetes in nonobese diabetic mice despite isotype-specific differences in Fc gamma R effector functions. J. Immunol. (Baltim., Md: 1950) 180, 2863–2875 (2008) Y. Xiu, C.P. Wong, J.D. Bouaziz, Y. Hamaguchi, Y. Wang, S.M. Pop, R.M. Tisch, T.F. Tedder, B lymphocyte depletion by CD20 monoclonal antibody prevents diabetes in nonobese diabetic mice despite isotype-specific differences in Fc gamma R effector functions. J. Immunol. (Baltim., Md: 1950) 180, 2863–2875 (2008)
25.
Zurück zum Zitat C.Y. Hu, D. Rodriguez-Pinto, W. Du, A. Ahuja, O. Henegariu, F.S. Wong, M.J. Shlomchik, L. Wen, Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. J. Clin. Investig. 117, 3857–3867 (2007)CrossRef C.Y. Hu, D. Rodriguez-Pinto, W. Du, A. Ahuja, O. Henegariu, F.S. Wong, M.J. Shlomchik, L. Wen, Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. J. Clin. Investig. 117, 3857–3867 (2007)CrossRef
26.
Zurück zum Zitat T.S. Olson, G. Bamias, M. Naganuma, J. Rivera-Nieves, T.L. Burcin, W. Ross, M.A. Morris, T.T. Pizarro, P.B. Ernst, F. Cominelli, K. Ley, Expanded B cell population blocks regulatory T cells and exacerbates ileitis in a murine model of Crohn disease. J. Clin. Investig. 114, 389–398 (2004)CrossRef T.S. Olson, G. Bamias, M. Naganuma, J. Rivera-Nieves, T.L. Burcin, W. Ross, M.A. Morris, T.T. Pizarro, P.B. Ernst, F. Cominelli, K. Ley, Expanded B cell population blocks regulatory T cells and exacerbates ileitis in a murine model of Crohn disease. J. Clin. Investig. 114, 389–398 (2004)CrossRef
27.
Zurück zum Zitat J.L. Quinn, R.C. Axtell, Emerging Role of Follicular T Helper cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Int. J. Mol. Sci 19, 3233 (2018).CrossRef J.L. Quinn, R.C. Axtell, Emerging Role of Follicular T Helper cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Int. J. Mol. Sci 19, 3233 (2018).CrossRef
28.
Zurück zum Zitat S.A. Olalekan, Y. Cao, K.M. Hamel, A. Finnegan, B cells expressing IFN-γ suppress Treg-cell differentiation and promote autoimmune experimental arthritis. Eur. J. Immunol. 45, 988–998 (2015)CrossRef S.A. Olalekan, Y. Cao, K.M. Hamel, A. Finnegan, B cells expressing IFN-γ suppress Treg-cell differentiation and promote autoimmune experimental arthritis. Eur. J. Immunol. 45, 988–998 (2015)CrossRef
29.
Zurück zum Zitat A. Bar-Or, L. Fawaz, B. Fan, P.J. Darlington, A. Rieger, C. Ghorayeb, P.A. Calabresi, E. Waubant, S.L. Hauser, J. Zhang, C.H. Smith, Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann. Neurol. 67, 452–461 (2010)CrossRef A. Bar-Or, L. Fawaz, B. Fan, P.J. Darlington, A. Rieger, C. Ghorayeb, P.A. Calabresi, E. Waubant, S.L. Hauser, J. Zhang, C.H. Smith, Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann. Neurol. 67, 452–461 (2010)CrossRef
30.
Zurück zum Zitat X. Lin, L. Lu, B cell-mediated autoimmune diseases. Adv. Exp. Med. Biol. 1254, 145–160 (2020)CrossRef X. Lin, L. Lu, B cell-mediated autoimmune diseases. Adv. Exp. Med. Biol. 1254, 145–160 (2020)CrossRef
31.
Zurück zum Zitat D. Bhatia, A. Sinha, P. Hari, S. Sopory, S. Saini, M. Puraswani, H. Saini, D.K. Mitra, A. Bagga, Rituximab modulates T- and B-lymphocyte subsets and urinary CD80 excretion in patients with steroid-dependent nephrotic syndrome. Pediatr. Res. 84, 520–526 (2018)CrossRef D. Bhatia, A. Sinha, P. Hari, S. Sopory, S. Saini, M. Puraswani, H. Saini, D.K. Mitra, A. Bagga, Rituximab modulates T- and B-lymphocyte subsets and urinary CD80 excretion in patients with steroid-dependent nephrotic syndrome. Pediatr. Res. 84, 520–526 (2018)CrossRef
32.
Zurück zum Zitat C. Hu, H. Ding, X. Zhang, F.S. Wong, L. Wen, Combination treatment with anti-CD20 and oral anti-CD3 prevents and reverses autoimmune diabetes. Diabetes 62, 2849–2858 (2013)CrossRef C. Hu, H. Ding, X. Zhang, F.S. Wong, L. Wen, Combination treatment with anti-CD20 and oral anti-CD3 prevents and reverses autoimmune diabetes. Diabetes 62, 2849–2858 (2013)CrossRef
33.
Zurück zum Zitat J. Lu, J. Liu, L. Li, Y. Lan, Y. Liang, Cytokines in type 1 diabetes: mechanisms of action and immunotherapeutic targets. Clin. Transl. Immunol. 9, e1122 (2020)CrossRef J. Lu, J. Liu, L. Li, Y. Lan, Y. Liang, Cytokines in type 1 diabetes: mechanisms of action and immunotherapeutic targets. Clin. Transl. Immunol. 9, e1122 (2020)CrossRef
34.
Zurück zum Zitat J.A. Emamaullee, J. Davis, S. Merani, C. Toso, J.F. Elliott, A. Thiesen, A.M. Shapiro, Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice. Diabetes 58, 1302–1311 (2009)CrossRef J.A. Emamaullee, J. Davis, S. Merani, C. Toso, J.F. Elliott, A. Thiesen, A.M. Shapiro, Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice. Diabetes 58, 1302–1311 (2009)CrossRef
35.
Zurück zum Zitat C.L. Langrish, Y. Chen, W.M. Blumenschein, J. Mattson, B. Basham, J.D. Sedgwick, T. McClanahan, R.A. Kastelein, D.J. Cua, IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201, 233–240 (2005)CrossRef C.L. Langrish, Y. Chen, W.M. Blumenschein, J. Mattson, B. Basham, J.D. Sedgwick, T. McClanahan, R.A. Kastelein, D.J. Cua, IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201, 233–240 (2005)CrossRef
36.
Zurück zum Zitat E.P. Mensah-Brown, A. Shahin, M. Al-Shamisi, X. Wei, M.L. Lukic, IL-23 leads to diabetes induction after subdiabetogenic treatment with multiple low doses of streptozotocin. Eur. J. Immunol. 36, 216–223 (2006)CrossRef E.P. Mensah-Brown, A. Shahin, M. Al-Shamisi, X. Wei, M.L. Lukic, IL-23 leads to diabetes induction after subdiabetogenic treatment with multiple low doses of streptozotocin. Eur. J. Immunol. 36, 216–223 (2006)CrossRef
37.
Zurück zum Zitat F. Abbasi, P. Amiri, F.A. Sayahpour, S. Pirmoradi, M. Abolhalaj, B. Larijani, J.T. Bazzaz, M.M. Amoli, TGF-β and IL-23 gene expression in unstimulated PBMCs of patients with diabetes. Endocrine 41, 430–434 (2012)CrossRef F. Abbasi, P. Amiri, F.A. Sayahpour, S. Pirmoradi, M. Abolhalaj, B. Larijani, J.T. Bazzaz, M.M. Amoli, TGF-β and IL-23 gene expression in unstimulated PBMCs of patients with diabetes. Endocrine 41, 430–434 (2012)CrossRef
38.
Zurück zum Zitat C. Li, L. Zhang, Y. Chen, X. Lin, T. Li, Protective role of adenovirus vector-mediated interleukin-10 gene therapy on endogenous islet β-cells in recent-onset type 1 diabetes in NOD mice. Exp. Therapeutic Med. 11, 1625–1632 (2016)CrossRef C. Li, L. Zhang, Y. Chen, X. Lin, T. Li, Protective role of adenovirus vector-mediated interleukin-10 gene therapy on endogenous islet β-cells in recent-onset type 1 diabetes in NOD mice. Exp. Therapeutic Med. 11, 1625–1632 (2016)CrossRef
39.
Zurück zum Zitat S. Robert, C. Gysemans, T. Takiishi, H. Korf, I. Spagnuolo, G. Sebastiani, K. Van Huynegem, L. Steidler, S. Caluwaerts, P. Demetter, C.H. Wasserfall, M.A. Atkinson, F. Dotta, P. Rottiers, T.L. Van Belle, C. Mathieu, Oral delivery of glutamic acid decarboxylase (GAD)-65 and IL10 by Lactococcus lactis reverses diabetes in recent-onset NOD mice. Diabetes 63, 2876–2887 (2014)CrossRef S. Robert, C. Gysemans, T. Takiishi, H. Korf, I. Spagnuolo, G. Sebastiani, K. Van Huynegem, L. Steidler, S. Caluwaerts, P. Demetter, C.H. Wasserfall, M.A. Atkinson, F. Dotta, P. Rottiers, T.L. Van Belle, C. Mathieu, Oral delivery of glutamic acid decarboxylase (GAD)-65 and IL10 by Lactococcus lactis reverses diabetes in recent-onset NOD mice. Diabetes 63, 2876–2887 (2014)CrossRef
40.
Zurück zum Zitat S. Kleffel, A. Vergani, S. Tezza, M. Ben Nasr, M.A. Niewczas, S. Wong, R. Bassi, F. D’Addio, T. Schatton, R. Abdi, M. Atkinson, M.H. Sayegh, L. Wen, C.H. Wasserfall, K.C. O’Connor, P. Fiorina, Interleukin-10+ regulatory B cells arise within antigen-experienced CD40+ B cells to maintain tolerance to islet autoantigens. Diabetes 64, 158–171 (2015)CrossRef S. Kleffel, A. Vergani, S. Tezza, M. Ben Nasr, M.A. Niewczas, S. Wong, R. Bassi, F. D’Addio, T. Schatton, R. Abdi, M. Atkinson, M.H. Sayegh, L. Wen, C.H. Wasserfall, K.C. O’Connor, P. Fiorina, Interleukin-10+ regulatory B cells arise within antigen-experienced CD40+ B cells to maintain tolerance to islet autoantigens. Diabetes 64, 158–171 (2015)CrossRef
41.
Zurück zum Zitat Peng Y., Laouar Y., Li M.O., Green E.A., Flavell R.A. TGF-beta regulates in vivo expansion of Foxp3-expressing CD4+CD25+ regulatory T cells responsible for protection against diabetes. Proc. Natl. Acad. Sci. USA101,4572-7(2004). Peng Y., Laouar Y., Li M.O., Green E.A., Flavell R.A. TGF-beta regulates in vivo expansion of Foxp3-expressing CD4+CD25+ regulatory T cells responsible for protection against diabetes. Proc. Natl. Acad. Sci. USA101,4572-7(2004).
Metadaten
Titel
Anti-CD20 therapy ameliorates β cell function and rebalances Th17/Treg cells in NOD mice
verfasst von
Min Chen
Qianhui Zhang
Yanhong Wei
Qianqian Wan
Min Xu
Xiaoqi Chen
Publikationsdatum
24.01.2022
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 1/2022
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-021-02965-x

Weitere Artikel der Ausgabe 1/2022

Endocrine 1/2022 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.