Invariant natural killer T cells and TGF-ß attenuate anti-GBM glomerulonephritis
2009
Mesnard, L. | Keller, A.D.C. | Michel, M.L. | Vandermeersch, S. | Rafat, C. | Letavernier, E. | Tillet, Yves | Rondeau, E. | Leite-De-Moraes, M.C. | Institut National de la Santé et de la Recherche Médicale (INSERM) | CHU Tenon [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) | Faculté de Médecine ; Université de Ngozi [Burundi] | Centre National de la Recherche Scientifique (CNRS) | Universidade de São Paulo = University of São Paulo (USP) | Physiologie de la reproduction et des comportements [Nouzilly] (PRC) ; Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
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Show more [+] Less [-]English. Invariant natural killer T (iNKT) cells represent a particular subset of T lymphocytes capable of producing several cytokines, which exert regulatory or effector functions, following stimulation of the T cell receptor. In this study, we investigated the influence of iNKT cells on the development of experimental anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). After injection of anti-GBM serum, the number of kidney iNKT cells rapidly increased. iNKT cell-deficient mice (J alpha 18(-/-)) injected with anti-GBM serum demonstrated worse renal function, increased proteinuria, and greater glomerular and tubular injury compared with similarly treated wild-type mice. We did not detect significant differences in Th1/Th2 polarization in renal tissue that might have explained the severity of disease in J alpha 18(-/-) mice. Interestingly, expression of both TGF-beta and TGF-beta-induced (TGFBI) mRNA was higher in wild-type kidneys compared with J alpha 18(-/-) kidneys, suggesting a possible protective role for TGF-beta in anti-GBM GN. Administration of an anti-TGF-beta neutralizing antibody significantly enhanced the severity of disease in wild-type, but not J alpha 18(-/-), mice. In conclusion, in experimental anti-GBM GN, iNKT cells attenuate disease severity and TGF-beta has a renoprotective role.
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