title: Interleukin-17A promotes early but attenuates established disease in crescentic glomerulonephritis in mice.
abstract: T helper (Th)17 cells might contribute to immune-mediated renal injury. Thus, we sought to define the time course of IL-17A-induced kidney damage and examined the relation between Th17 and Th1 cells in a model of crescentic anti-glomerular basement membrane glomerulonephritis. Renal injury and immune responses were assessed in wild-type and in IL-17A-deficient mice on days 6, 14, and 21 of disease development. On day 6, when mild glomerulonephritis developed, IL-17A-deficient mice were protected from renal injury. On day 14, when more severe disease developed, protection from renal injury due to IL-17A deficiency was less evident. On day 21, when crescentic glomerulonephritis was fully established, disease was enhanced in IL-17A(-/-) mice, with increased glomerular T-cell accumulation and fibrin deposition, and augmented Th1 responses. Mice lacking the Th17-promoting cytokine, IL-23 (p19), also developed more severe disease than wild-type animals on day 21. In contrast, mice deficient in the key Th1-promoting cytokine, IL-12 (p35), had decreased Th1 and increased Th17 responses and developed less severe crescentic glomerulonephritis than wild-type animals. These studies show that IL-17A contributes to early glomerular injury, but it attenuates established crescentic glomerulonephritis by suppressing Th1 responses. They provide further evidence that Th1 cells mediate crescentic injury in this model and that Th1 and Th17 cells counterregulate each other during disease development.
authors: Department of Medicine, Centre for Inflammatory Diseases, Monash University, Monash Medical Centre, Clayton, Australia.
authors: Dragana
authors: D
authors: Odobasic
authors: Poh-Yi
authors: PY
authors: Gan
authors: Shaun A
authors: SA
authors: Summers
authors: Tim J
authors: TJ
authors: Semple
authors: Ruth C M
authors: RC
authors: Muljadi
authors: Yoichiro
authors: Y
authors: Iwakura
authors: A Richard
authors: AR
authors: Kitching
authors: Stephen R
authors: SR
authors: Holdsworth
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology*; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002470:Cell Survival; D005337:Fibrin / Q000378:metabolism; D007111:Immunity, Cellular / Q000276:immunology; D007136:Immunoglobulins; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000172:deficiency; D020381:Interleukin-17 / Q000172:deficiency* / Q000378:metabolism; D053759:Interleukin-23 / Q000172:deficiency / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D020381:Interleukin-17; D053759:Interleukin-23; D018664:Interleukin-12; D007371:Interferon-gamma; D005337:Fibrin