title: Regulation of pathogenic Th17 cell differentiation by IL-10 in the development of glomerulonephritis.
abstract: Although it is clear that T helper (Th)17 cells play a pathologic role in the pathogenesis of several inflammatory diseases, the contribution and regulation of pathogenic Th17 cells in the development of glomerulonephritis are still not fully understood. Herein, we show that IL-10-deficient mice exhibit exacerbation of glomerulonephritis after induction with anti-glomerular basement membrane globulin, with enhanced pathogenic Th17 immune responses. We further demonstrate that Rag1(-/-) mice reconstituted with IL-10(-/-) CD4(+) T cells develop more severe glomerulonephritis after induction of anti-glomerular basement membrane disease, with more infiltration of inflammatory cells into the kidneys. Finally, IL-17 and interferon γ double-positive cells were significantly increased in IL-10(-/-) CD4(+) T-cell cultures under pathogenic Th17 conditions compared with wild-type cell cultures. These findings suggest that T-cell-derived IL-10 plays a critical suppressive role in the control of pathogenic Th17 cell differentiation and highlights the importance of IL-10 as protection against glomerulonephritis development.
authors.affiliation: Immunology Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029-6574, USA.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Zhang
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Chuang
authors.forename: Geming
authors.initials: G
authors.lastname: Lu
authors.forename: Ruijie
authors.initials: R
authors.lastname: Liu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yang
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
authors.forename: Yan
authors.initials: Y
authors.lastname: Dai
authors.forename: Zihan
authors.initials: Z
authors.lastname: Zheng
authors.forename: Chen-Feng
authors.initials: CF
authors.lastname: Qi
authors.forename: John Cijiang
authors.initials: JC
authors.lastname: He
authors.forename: Huabao
authors.initials: H
authors.lastname: Xiong
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000633:toxicity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D018398:Homeodomain Proteins / Q000378:metabolism; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000172:deficiency* / Q000502:physiology; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D058504:Th17 Cells / Q000276:immunology / Q000473:pathology*
chemical_list: D001323:Autoantibodies; D018398:Homeodomain Proteins; D020381:Interleukin-17; C051951:antiglomerular basement membrane antibody; C064658:RAG-1 protein; D016753:Interleukin-10; D007371:Interferon-gamma