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Published in: Arthritis Research & Therapy 1/2012

Open Access 01-02-2012 | Research article

Interleukin-10 produced by B cells is crucial for the suppression of Th17/Th1 responses, induction of T regulatory type 1 cells and reduction of collagen-induced arthritis

Authors: Natalie A Carter, Elizabeth C Rosser, Claudia Mauri

Published in: Arthritis Research & Therapy | Issue 1/2012

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Abstract

Introduction

Interleukin-10 (IL-10) producing B cells, also known as regulatory B (Breg) cells, play a key role in controlling autoimmunity. Our laboratory and others have demonstrated a pivotal role for Bregs in rheumatological disorders, including experimental models of arthritis and lupus. The aim of this study was to identify the role of endogenous IL-10 secreting B cells in vivo in controlling the induction and disease progression of collagen-induced arthritis (CIA).

Methods

We generated chimeric mice that had IL-10 knocked-out specifically in the B cell population. These mice were compared with wild-type (WT) B cell chimeric mice for their susceptibility to CIA.

Results

Here we report that chimeric mice specifically lacking IL-10 producing B cells (IL-10-/- B cell) developed an exacerbated CIA compared to chimeric wild type B cell (WT B cell) mice. A marked increase in inflammatory Th1 and Th17 cells were detected in IL-10-/-B cell mice compared to WT B cell mice. Furthermore, there was a reduction in IL-10 secreting CD4+ Tr1 cells in these animals.

Conclusions

IL-10 producing B cells restrain inflammation by promoting differentiation of immuno-regulatory over pro-inflammatory T cells and, hence, act to maintain tolerance.
Appendix
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Literature
1.
go back to reference Mauri C, Williams RO, Walmsley M, Feldmann M: Relationship between Th1/Th2 cytokine patterns and the arthritogenic response in collagen-induced arthritis. Eur J Immunol. 1996, 26: 1511-1518. 10.1002/eji.1830260716.CrossRefPubMed Mauri C, Williams RO, Walmsley M, Feldmann M: Relationship between Th1/Th2 cytokine patterns and the arthritogenic response in collagen-induced arthritis. Eur J Immunol. 1996, 26: 1511-1518. 10.1002/eji.1830260716.CrossRefPubMed
2.
go back to reference Mauritz NJ, Holmdahl R, Jonsson R, Van der Meide PH, Scheynius A, Klareskog L: Treatment with gamma-interferon triggers the onset of collagen arthritis in mice. Arthritis Rheum. 1988, 31: 1297-1304. 10.1002/art.1780311012.CrossRefPubMed Mauritz NJ, Holmdahl R, Jonsson R, Van der Meide PH, Scheynius A, Klareskog L: Treatment with gamma-interferon triggers the onset of collagen arthritis in mice. Arthritis Rheum. 1988, 31: 1297-1304. 10.1002/art.1780311012.CrossRefPubMed
3.
go back to reference Germann T, Szeliga J, Hess H, Storkel S, Podlaski FJ, Gately MK, Schmitt E, Rude E: Administration of interleukin 12 in combination with type II collagen induces severe arthritis in DBA/1 mice. Proc Natl Acad Sci USA. 1995, 92: 4823-4827. 10.1073/pnas.92.11.4823.PubMedCentralCrossRefPubMed Germann T, Szeliga J, Hess H, Storkel S, Podlaski FJ, Gately MK, Schmitt E, Rude E: Administration of interleukin 12 in combination with type II collagen induces severe arthritis in DBA/1 mice. Proc Natl Acad Sci USA. 1995, 92: 4823-4827. 10.1073/pnas.92.11.4823.PubMedCentralCrossRefPubMed
4.
go back to reference Mussener A, Litton MJ, Lindroos E, Klareskog L: Cytokine production in synovial tissue of mice with collagen-induced arthritis (CIA). Clin Exp Immunol. 1997, 107: 485-493. 10.1046/j.1365-2249.1997.3181214.x.PubMedCentralCrossRefPubMed Mussener A, Litton MJ, Lindroos E, Klareskog L: Cytokine production in synovial tissue of mice with collagen-induced arthritis (CIA). Clin Exp Immunol. 1997, 107: 485-493. 10.1046/j.1365-2249.1997.3181214.x.PubMedCentralCrossRefPubMed
5.
go back to reference Stasiuk LM, Abehsira-Amar O, Fournier C: Collagen-induced arthritis in DBA/1 mice: cytokine gene activation following immunization with type II collagen. Cell Immunol. 1996, 173: 269-275. 10.1006/cimm.1996.0277.CrossRefPubMed Stasiuk LM, Abehsira-Amar O, Fournier C: Collagen-induced arthritis in DBA/1 mice: cytokine gene activation following immunization with type II collagen. Cell Immunol. 1996, 173: 269-275. 10.1006/cimm.1996.0277.CrossRefPubMed
6.
go back to reference Holmdahl R, Jansson L, Larsson A, Jonsson R: Arthritis in DBA/1 mice induced with passively transferred type II collagen immune serum. Immunohistopathology and serum levels of anti-type II collagen auto-antibodies. Scand J Immunol. 1990, 31: 147-157. 10.1111/j.1365-3083.1990.tb02754.x.CrossRefPubMed Holmdahl R, Jansson L, Larsson A, Jonsson R: Arthritis in DBA/1 mice induced with passively transferred type II collagen immune serum. Immunohistopathology and serum levels of anti-type II collagen auto-antibodies. Scand J Immunol. 1990, 31: 147-157. 10.1111/j.1365-3083.1990.tb02754.x.CrossRefPubMed
7.
go back to reference Stuart JM, Tomoda K, Yoo TJ, Townes AS, Kang AH: Serum transfer of collagen-induced arthritis. II. Identification and localization of autoantibody to type II collagen in donor and recipient rats. Arthritis Rheum. 1983, 26: 1237-1244. 10.1002/art.1780261011.CrossRefPubMed Stuart JM, Tomoda K, Yoo TJ, Townes AS, Kang AH: Serum transfer of collagen-induced arthritis. II. Identification and localization of autoantibody to type II collagen in donor and recipient rats. Arthritis Rheum. 1983, 26: 1237-1244. 10.1002/art.1780261011.CrossRefPubMed
8.
go back to reference Svensson L, Jirholt J, Holmdahl R, Jansson L: B cell-deficient mice do not develop type II collagen-induced arthritis (CIA). Clin Exp Immunol. 1998, 111: 521-526. 10.1046/j.1365-2249.1998.00529.x.PubMedCentralCrossRefPubMed Svensson L, Jirholt J, Holmdahl R, Jansson L: B cell-deficient mice do not develop type II collagen-induced arthritis (CIA). Clin Exp Immunol. 1998, 111: 521-526. 10.1046/j.1365-2249.1998.00529.x.PubMedCentralCrossRefPubMed
9.
go back to reference Evans JG, Chavez-Rueda KA, Eddaoudi A, Meyer-Bahlburg A, Rawlings DJ, Ehrenstein MR, Mauri C: Novel suppressive function of transitional 2 B cells in experimental arthritis. J Immunol. 2007, 178: 7868-7878.CrossRefPubMed Evans JG, Chavez-Rueda KA, Eddaoudi A, Meyer-Bahlburg A, Rawlings DJ, Ehrenstein MR, Mauri C: Novel suppressive function of transitional 2 B cells in experimental arthritis. J Immunol. 2007, 178: 7868-7878.CrossRefPubMed
10.
go back to reference Mauri C, Gray D, Mushtaq N, Londei M: Prevention of arthritis by interleukin 10-producing B cells. J Exp Med. 2003, 197: 489-501. 10.1084/jem.20021293.PubMedCentralCrossRefPubMed Mauri C, Gray D, Mushtaq N, Londei M: Prevention of arthritis by interleukin 10-producing B cells. J Exp Med. 2003, 197: 489-501. 10.1084/jem.20021293.PubMedCentralCrossRefPubMed
11.
go back to reference Keravala A, Lechman ER, Nash J, Mi Z, Robbins PD: Human, viral or mutant human IL-10 expressed after local adenovirus-mediated gene transfer are equally effective in ameliorating disease pathology in a rabbit knee model of antigen-induced arthritis. Arthritis Res Ther. 2006, 8: R91-10.1186/ar1960.PubMedCentralCrossRefPubMed Keravala A, Lechman ER, Nash J, Mi Z, Robbins PD: Human, viral or mutant human IL-10 expressed after local adenovirus-mediated gene transfer are equally effective in ameliorating disease pathology in a rabbit knee model of antigen-induced arthritis. Arthritis Res Ther. 2006, 8: R91-10.1186/ar1960.PubMedCentralCrossRefPubMed
12.
go back to reference Finnegan A, Kaplan CD, Cao Y, Eibel H, Glant TT, Zhang J: Collagen-induced arthritis is exacerbated in IL-10-deficient mice. Arthritis Res Ther. 2003, 5: R18-24. 10.1186/ar601.PubMedCentralCrossRefPubMed Finnegan A, Kaplan CD, Cao Y, Eibel H, Glant TT, Zhang J: Collagen-induced arthritis is exacerbated in IL-10-deficient mice. Arthritis Res Ther. 2003, 5: R18-24. 10.1186/ar601.PubMedCentralCrossRefPubMed
13.
go back to reference Johansson AC, Hansson AS, Nandakumar KS, Backlund J, Holmdahl R: IL-10-deficient B10.Q mice develop more severe collagen-induced arthritis, but are protected from arthritis induced with anti-type II collagen antibodies. J Immunol. 2001, 167: 3505-3512.CrossRefPubMed Johansson AC, Hansson AS, Nandakumar KS, Backlund J, Holmdahl R: IL-10-deficient B10.Q mice develop more severe collagen-induced arthritis, but are protected from arthritis induced with anti-type II collagen antibodies. J Immunol. 2001, 167: 3505-3512.CrossRefPubMed
14.
go back to reference Bacchetta R, Bigler M, Touraine JL, Parkman R, Tovo PA, Abrams J, de Waal Malefyt R, de Vries JE, Roncarolo MG: High levels of interleukin 10 production in vivo are associated with tolerance in SCID patients transplanted with HLA mismatched hematopoietic stem cells. J Exp Med. 1994, 179: 493-502. 10.1084/jem.179.2.493.CrossRefPubMed Bacchetta R, Bigler M, Touraine JL, Parkman R, Tovo PA, Abrams J, de Waal Malefyt R, de Vries JE, Roncarolo MG: High levels of interleukin 10 production in vivo are associated with tolerance in SCID patients transplanted with HLA mismatched hematopoietic stem cells. J Exp Med. 1994, 179: 493-502. 10.1084/jem.179.2.493.CrossRefPubMed
15.
go back to reference Bettelli E, Das MP, Howard ED, Weiner HL, Sobel RA, Kuchroo VK: IL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10- and IL-4-deficient and transgenic mice. J Immunol. 1998, 161: 3299-3306.PubMed Bettelli E, Das MP, Howard ED, Weiner HL, Sobel RA, Kuchroo VK: IL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10- and IL-4-deficient and transgenic mice. J Immunol. 1998, 161: 3299-3306.PubMed
16.
go back to reference Davidson NJ, Fort MM, Muller W, Leach MW, Rennick DM: Chronic colitis in IL-10-/- mice: insufficient counter regulation of a Th1 response. Int Rev Immunol. 2000, 19: 91-121. 10.3109/08830180009048392.CrossRefPubMed Davidson NJ, Fort MM, Muller W, Leach MW, Rennick DM: Chronic colitis in IL-10-/- mice: insufficient counter regulation of a Th1 response. Int Rev Immunol. 2000, 19: 91-121. 10.3109/08830180009048392.CrossRefPubMed
17.
go back to reference Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM: B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 2002, 3: 944-950.CrossRefPubMed Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM: B cells regulate autoimmunity by provision of IL-10. Nat Immunol. 2002, 3: 944-950.CrossRefPubMed
18.
go back to reference Suri-Payer E, Fritzsching B: Regulatory T cells in experimental autoimmune disease. Springer Semin Immunopathol. 2006, 28: 3-16. 10.1007/s00281-006-0021-8.CrossRefPubMed Suri-Payer E, Fritzsching B: Regulatory T cells in experimental autoimmune disease. Springer Semin Immunopathol. 2006, 28: 3-16. 10.1007/s00281-006-0021-8.CrossRefPubMed
19.
go back to reference Carter NA, Vasconcellos R, Rosser EC, Tulone C, Munoz-Suano A, Kamanaka M, Ehrenstein MR, Flavell RA, Mauri C: Mice lacking endogenous IL-10-producing regulatory B cells develop exacerbated disease and present with an increased frequency of Th1/Th17 but a decrease in regulatory T cells. J Immunol. 2011, 186: 5569-5579. 10.4049/jimmunol.1100284.CrossRefPubMed Carter NA, Vasconcellos R, Rosser EC, Tulone C, Munoz-Suano A, Kamanaka M, Ehrenstein MR, Flavell RA, Mauri C: Mice lacking endogenous IL-10-producing regulatory B cells develop exacerbated disease and present with an increased frequency of Th1/Th17 but a decrease in regulatory T cells. J Immunol. 2011, 186: 5569-5579. 10.4049/jimmunol.1100284.CrossRefPubMed
20.
go back to reference Yanaba K, Bouaziz JD, Haas KM, Poe JC, Fujimoto M, Tedder TF: A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity. 2008, 28: 639-650. 10.1016/j.immuni.2008.03.017.CrossRefPubMed Yanaba K, Bouaziz JD, Haas KM, Poe JC, Fujimoto M, Tedder TF: A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity. 2008, 28: 639-650. 10.1016/j.immuni.2008.03.017.CrossRefPubMed
21.
go back to reference Bouaziz JD, Yanaba K, Tedder TF: Regulatory B cells as inhibitors of immune responses and inflammation. Immunol Rev. 2008, 224: 201-214. 10.1111/j.1600-065X.2008.00661.x.CrossRefPubMed Bouaziz JD, Yanaba K, Tedder TF: Regulatory B cells as inhibitors of immune responses and inflammation. Immunol Rev. 2008, 224: 201-214. 10.1111/j.1600-065X.2008.00661.x.CrossRefPubMed
22.
go back to reference Matsushita T, Yanaba K, Bouaziz JD, Fujimoto M, Tedder TF: Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J Clin Invest. 2008, 118: 3420-3430.PubMedCentralPubMed Matsushita T, Yanaba K, Bouaziz JD, Fujimoto M, Tedder TF: Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J Clin Invest. 2008, 118: 3420-3430.PubMedCentralPubMed
23.
go back to reference Mauri C, Ehrenstein MR: The 'short' history of regulatory B cells. Trends Immunol. 2008, 29: 34-40. 10.1016/j.it.2007.10.004.CrossRefPubMed Mauri C, Ehrenstein MR: The 'short' history of regulatory B cells. Trends Immunol. 2008, 29: 34-40. 10.1016/j.it.2007.10.004.CrossRefPubMed
24.
go back to reference Watanabe R, Fujimoto M, Ishiura N, Kuwano Y, Nakashima H, Yazawa N, Okochi H, Sato S, Tedder TF, Tamaki K: CD19 expression in B cells is important for suppression of contact hypersensitivity. Am J Pathol. 2007, 171: 560-570. 10.2353/ajpath.2007.061279.PubMedCentralCrossRefPubMed Watanabe R, Fujimoto M, Ishiura N, Kuwano Y, Nakashima H, Yazawa N, Okochi H, Sato S, Tedder TF, Tamaki K: CD19 expression in B cells is important for suppression of contact hypersensitivity. Am J Pathol. 2007, 171: 560-570. 10.2353/ajpath.2007.061279.PubMedCentralCrossRefPubMed
25.
go back to reference Watanabe R, Ishiura N, Nakashima H, Kuwano Y, Okochi H, Tamaki K, Sato S, Tedder TF, Fujimoto M: Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity. J Immunol. 2010, 184: 4801-4809. 10.4049/jimmunol.0902385.PubMedCentralCrossRefPubMed Watanabe R, Ishiura N, Nakashima H, Kuwano Y, Okochi H, Tamaki K, Sato S, Tedder TF, Fujimoto M: Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity. J Immunol. 2010, 184: 4801-4809. 10.4049/jimmunol.0902385.PubMedCentralCrossRefPubMed
26.
go back to reference Brackertz D, Mitchell GF, Mackay IR: Antigen-induced arthritis in mice. I. Induction of arthritis in various strains of mice. Arthritis Rheum. 1977, 20: 841-850. 10.1002/art.1780200314.CrossRefPubMed Brackertz D, Mitchell GF, Mackay IR: Antigen-induced arthritis in mice. I. Induction of arthritis in various strains of mice. Arthritis Rheum. 1977, 20: 841-850. 10.1002/art.1780200314.CrossRefPubMed
27.
go back to reference Boe A, Baiocchi M, Carbonatto M, Papoian R, Serlupi-Crescenzi O: Interleukin 6 knock-out mice are resistant to antigen-induced experimental arthritis. Cytokine. 1999, 11: 1057-1064. 10.1006/cyto.1999.0502.CrossRefPubMed Boe A, Baiocchi M, Carbonatto M, Papoian R, Serlupi-Crescenzi O: Interleukin 6 knock-out mice are resistant to antigen-induced experimental arthritis. Cytokine. 1999, 11: 1057-1064. 10.1006/cyto.1999.0502.CrossRefPubMed
28.
go back to reference Busso N, Frasnelli M, Feifel R, Cenni B, Steinhoff M, Hamilton J, So A: Evaluation of protease-activated receptor 2 in murine models of arthritis. Arthritis Rheum. 2007, 56: 101-107. 10.1002/art.22312.CrossRefPubMed Busso N, Frasnelli M, Feifel R, Cenni B, Steinhoff M, Hamilton J, So A: Evaluation of protease-activated receptor 2 in murine models of arthritis. Arthritis Rheum. 2007, 56: 101-107. 10.1002/art.22312.CrossRefPubMed
29.
go back to reference Williams RO, Mauri C, Mason LJ, Marinova-Mutafchieva L, Ross SE, Feldmann M, Maini RN: Therapeutic actions of cyclosporine and anti-tumor necrosis factor alpha in collagen-induced arthritis and the effect of combination therapy. Arthritis Rheum. 1998, 41: 1806-1812. 10.1002/1529-0131(199810)41:10<1806::AID-ART12>3.0.CO;2-9.CrossRefPubMed Williams RO, Mauri C, Mason LJ, Marinova-Mutafchieva L, Ross SE, Feldmann M, Maini RN: Therapeutic actions of cyclosporine and anti-tumor necrosis factor alpha in collagen-induced arthritis and the effect of combination therapy. Arthritis Rheum. 1998, 41: 1806-1812. 10.1002/1529-0131(199810)41:10<1806::AID-ART12>3.0.CO;2-9.CrossRefPubMed
30.
go back to reference Berg DJ, Davidson N, Kuhn R, Muller W, Menon S, Holland G, Thompson-Snipes L, Leach MW, Rennick D: Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest. 1996, 98: 1010-1020. 10.1172/JCI118861.PubMedCentralCrossRefPubMed Berg DJ, Davidson N, Kuhn R, Muller W, Menon S, Holland G, Thompson-Snipes L, Leach MW, Rennick D: Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest. 1996, 98: 1010-1020. 10.1172/JCI118861.PubMedCentralCrossRefPubMed
31.
go back to reference Rennick DM, Fort MM: Lessons from genetically engineered animal models. XII. IL-10-deficient (IL-10(-/-) mice and intestinal inflammation. Am J Physiol Gastrointest Liver Physiol. 2000, 278: G829-833.PubMed Rennick DM, Fort MM: Lessons from genetically engineered animal models. XII. IL-10-deficient (IL-10(-/-) mice and intestinal inflammation. Am J Physiol Gastrointest Liver Physiol. 2000, 278: G829-833.PubMed
32.
go back to reference Feldmann M, Brennan FM, Maini RN: Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996, 14: 397-440. 10.1146/annurev.immunol.14.1.397.CrossRefPubMed Feldmann M, Brennan FM, Maini RN: Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996, 14: 397-440. 10.1146/annurev.immunol.14.1.397.CrossRefPubMed
33.
go back to reference Finkelman FD, Morris SC: Development of an assay to measure in vivo cytokine production in the mouse. Int Immunol. 1999, 11: 1811-1818. 10.1093/intimm/11.11.1811.CrossRefPubMed Finkelman FD, Morris SC: Development of an assay to measure in vivo cytokine production in the mouse. Int Immunol. 1999, 11: 1811-1818. 10.1093/intimm/11.11.1811.CrossRefPubMed
34.
go back to reference Blair PA, Chavez-Rueda KA, Evans JG, Shlomchik MJ, Eddaoudi A, Isenberg DA, Ehrenstein MR, Mauri C: Selective targeting of B cells with agonistic anti-CD40 is an efficacious strategy for the generation of induced regulatory T2-like B cells and for the suppression of lupus in MRL/lpr mice. J Immunol. 2009, 182: 3492-3502. 10.4049/jimmunol.0803052.PubMedCentralCrossRefPubMed Blair PA, Chavez-Rueda KA, Evans JG, Shlomchik MJ, Eddaoudi A, Isenberg DA, Ehrenstein MR, Mauri C: Selective targeting of B cells with agonistic anti-CD40 is an efficacious strategy for the generation of induced regulatory T2-like B cells and for the suppression of lupus in MRL/lpr mice. J Immunol. 2009, 182: 3492-3502. 10.4049/jimmunol.0803052.PubMedCentralCrossRefPubMed
35.
go back to reference Mizoguchi A, Mizoguchi E, Smith RN, Preffer FI, Bhan AK: Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice. J Exp Med. 1997, 186: 1749-1756. 10.1084/jem.186.10.1749.PubMedCentralCrossRefPubMed Mizoguchi A, Mizoguchi E, Smith RN, Preffer FI, Bhan AK: Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice. J Exp Med. 1997, 186: 1749-1756. 10.1084/jem.186.10.1749.PubMedCentralCrossRefPubMed
36.
go back to reference Wolf SD, Dittel BN, Hardardottir F, Janeway CA: Experimental autoimmune encephalomyelitis induction in genetically B cell-deficient mice. J Exp Med. 1996, 184: 2271-2278. 10.1084/jem.184.6.2271.PubMedCentralCrossRefPubMed Wolf SD, Dittel BN, Hardardottir F, Janeway CA: Experimental autoimmune encephalomyelitis induction in genetically B cell-deficient mice. J Exp Med. 1996, 184: 2271-2278. 10.1084/jem.184.6.2271.PubMedCentralCrossRefPubMed
37.
go back to reference Mauri C, Carter N: Is there a feudal hierarchy amongst regulatory immune cells? More than just Tregs. Arthritis Res Ther. 2009, 11: 237-10.1186/ar2752.PubMedCentralCrossRefPubMed Mauri C, Carter N: Is there a feudal hierarchy amongst regulatory immune cells? More than just Tregs. Arthritis Res Ther. 2009, 11: 237-10.1186/ar2752.PubMedCentralCrossRefPubMed
38.
go back to reference Awasthi A, Carrier Y, Peron JP, Bettelli E, Kamanaka M, Flavell RA, Kuchroo VK, Oukka M, Weiner HL: A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol. 2007, 8: 1380-1389. 10.1038/ni1541.CrossRefPubMed Awasthi A, Carrier Y, Peron JP, Bettelli E, Kamanaka M, Flavell RA, Kuchroo VK, Oukka M, Weiner HL: A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol. 2007, 8: 1380-1389. 10.1038/ni1541.CrossRefPubMed
39.
go back to reference Groux H, Cottrez F: The complex role of interleukin-10 in autoimmunity. J Autoimmun. 2003, 20: 281-285. 10.1016/S0896-8411(03)00044-1.CrossRefPubMed Groux H, Cottrez F: The complex role of interleukin-10 in autoimmunity. J Autoimmun. 2003, 20: 281-285. 10.1016/S0896-8411(03)00044-1.CrossRefPubMed
40.
go back to reference Levings MK, Gregori S, Tresoldi E, Cazzaniga S, Bonini C, Roncarolo MG: Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. Blood. 2005, 105: 1162-1169.CrossRefPubMed Levings MK, Gregori S, Tresoldi E, Cazzaniga S, Bonini C, Roncarolo MG: Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. Blood. 2005, 105: 1162-1169.CrossRefPubMed
41.
go back to reference Roncarolo MG, Bacchetta R, Bordignon C, Narula S, Levings MK: Type 1 T regulatory cells. Immunol Rev. 2001, 182: 68-79. 10.1034/j.1600-065X.2001.1820105.x.CrossRefPubMed Roncarolo MG, Bacchetta R, Bordignon C, Narula S, Levings MK: Type 1 T regulatory cells. Immunol Rev. 2001, 182: 68-79. 10.1034/j.1600-065X.2001.1820105.x.CrossRefPubMed
42.
go back to reference 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. 10.1111/j.0105-2896.2006.00420.x.CrossRefPubMed 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. 10.1111/j.0105-2896.2006.00420.x.CrossRefPubMed
43.
go back to reference Gray M, Miles K, Salter D, Gray D, Savill J: Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells. Proc Natl Acad Sci USA. 2007, 104: 14080-14085. 10.1073/pnas.0700326104.PubMedCentralCrossRefPubMed Gray M, Miles K, Salter D, Gray D, Savill J: Apoptotic cells protect mice from autoimmune inflammation by the induction of regulatory B cells. Proc Natl Acad Sci USA. 2007, 104: 14080-14085. 10.1073/pnas.0700326104.PubMedCentralCrossRefPubMed
44.
go back to reference Paust S, Lu L, McCarty N, Cantor H: Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc Natl Acad Sci USA. 2004, 101: 10398-10403. 10.1073/pnas.0403342101.PubMedCentralCrossRefPubMed Paust S, Lu L, McCarty N, Cantor H: Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc Natl Acad Sci USA. 2004, 101: 10398-10403. 10.1073/pnas.0403342101.PubMedCentralCrossRefPubMed
45.
go back to reference Dorner T, Burmester GR: The role of B cells in rheumatoid arthritis: mechanisms and therapeutic targets. Curr Opin Rheumatol. 2003, 15: 246-252. 10.1097/00002281-200305000-00011.CrossRefPubMed Dorner T, Burmester GR: The role of B cells in rheumatoid arthritis: mechanisms and therapeutic targets. Curr Opin Rheumatol. 2003, 15: 246-252. 10.1097/00002281-200305000-00011.CrossRefPubMed
46.
go back to reference Correale J, Farez M, Razzitte G: Helminth infections associated with multiple sclerosis induce regulatory B cells. Ann Neurol. 2008, 64: 187-199. 10.1002/ana.21438.CrossRefPubMed Correale J, Farez M, Razzitte G: Helminth infections associated with multiple sclerosis induce regulatory B cells. Ann Neurol. 2008, 64: 187-199. 10.1002/ana.21438.CrossRefPubMed
47.
go back to reference Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK: Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity. 2002, 16: 219-230. 10.1016/S1074-7613(02)00274-1.CrossRefPubMed Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK: Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity. 2002, 16: 219-230. 10.1016/S1074-7613(02)00274-1.CrossRefPubMed
Metadata
Title
Interleukin-10 produced by B cells is crucial for the suppression of Th17/Th1 responses, induction of T regulatory type 1 cells and reduction of collagen-induced arthritis
Authors
Natalie A Carter
Elizabeth C Rosser
Claudia Mauri
Publication date
01-02-2012
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2012
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar3736

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Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine