title: NOD mice contain an elevated frequency of iNKT17 cells that exacerbate diabetes.
abstract: Invariant natural killer T (iNKT) cells are a distinct lineage of innate-like T lymphocytes and converging studies in mouse models have demonstrated the protective role of iNKT cells in the development of type 1 diabetes. Recently, a new subset of iNKT cells, producing high levels of the pro-inflammatory cytokine IL-17, has been identified (iNKT17 cells). Since this cytokine has been implicated in several autoimmune diseases, we have analyzed iNKT17 cell frequency, absolute number and phenotypes in the pancreas and lymphoid organs in non-obese diabetic (NOD) mice. The role of iNKT17 cells in the development of diabetes was investigated using transfer experiments. NOD mice exhibit a higher frequency and absolute number of iNKT17 cells in the lymphoid organs as compared with C57BL/6 mice. iNKT17 cells infiltrate the pancreas of NOD mice where they express IL-17 mRNA. Contrary to the protective role of CD4(+)  iNKT cells, the CD4(-)  iNKT cell population, which contains iNKT17 cells, enhances the incidence of diabetes. Treatment with a blocking anti-IL-17 antibody prevents the exacerbation of the disease. This study reveals that different iNKT cell subsets play distinct roles in the regulation of type 1 diabetes and iNKT17 cells, which are abundant in NOD mice, exacerbate diabetes development.
authors: INSERM U986, Hôpital Cochin/Saint-Vincent de Paul, Paris, France.
authors: Yannick
authors: Y
authors: Simoni
authors: Anne-Sophie
authors: AS
authors: Gautron
authors: Lucie
authors: L
authors: Beaudoin
authors: Linh-Chi
authors: LC
authors: Bui
authors: Marie-Laure
authors: ML
authors: Michel
authors: Xavier
authors: X
authors: Coumoul
authors: Gérard
authors: G
authors: Eberl
authors: Maria
authors: M
authors: Leite-de-Moraes
authors: Agnès
authors: A
authors: Lehuen
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010179:Pancreas / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D015704:CD4 Antigens; D020381:Interleukin-17; D012333:RNA, Messenger