Pathogenic T helper type 17 cells contribute to type 1 diabetes independently of interleukin-22.
We have shown that pathogenic T helper type 17 (Th17) cells differentiated from naive CD4(+) T cells of BDC2·5 T cell receptor transgenic non-obese diabetic (NOD) mice by interleukin (IL)-23 plus IL-6 produce IL-17, IL-22 and induce type 1 diabetes (T1D). Neutralizing interferon (IFN)-γ during the polarization process leads to a significant increase in IL-22 production by these Th17 cells. We also isolated IL-22-producing Th17 cells from the pancreas of wild-type diabetic NOD mice. IL-27 also blocked IL-22 production from diabetogenic Th17 cells. To determine the functional role of IL-22 produced by pathogenic Th17 cells in T1D we neutralized IL-22 in vivo by using anti-IL-22 monoclonal antibody. We found that blocking IL-22 did not alter significantly adoptive transfer of disease by pathogenic Th17 cells. Therefore, IL-22 is not required for T1D pathogenesis. The IL-22Rα receptor for IL-22 however, increased in the pancreas of NOD mice during disease progression and based upon our and other studies we suggest that IL-22 may have a regenerative and protective role in the pancreatic islets.
Centre for Human Immunology and Department of Microbiology and Immunology and Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
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Bellemore
Centre for Human Immunology and Department of Microbiology and Immunology and Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
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Nikoopour
Centre for Human Immunology and Department of Microbiology and Immunology and Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
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Krougly
Centre for Human Immunology and Department of Microbiology and Immunology and Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
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Lee-Chan
Inflammation and Immunology, Biotherapeutics Research and Development, Pfizer Inc., Cambridge, MA, 02140, USA.
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Fouser
Centre for Human Immunology and Department of Microbiology and Immunology and Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
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Singh
D019264:Adoptive Transfer; D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D015551:Autoimmunity; D002454:Cell Differentiation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D007371:Interferon-gamma / Q000276:immunology; D064094:Interleukin-27 / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology*; D007515:Islets of Langerhans / Q000378:metabolism; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000276:immunology; D018123:Receptors, Interleukin / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D000097043:Interleukin-22
D019138:Antibodies, Blocking; D057134:Antibodies, Neutralizing; D007371:Interferon-gamma; D064094:Interleukin-27; D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C415369:interleukin-22 receptor
IL-22; Th17 cells; autoimmunity; type 1 diabetes