Invariant Natural Killer T Cells and TGF-beta Attenuate Anti-GBM Glomerulonephritis

Autor(es)

Mesnard, Laurent ^[1] ; Keller, Alexandre D. C. ^[2] ; Michel, Marie-Laure ^[3] ; Vandermeersch, Sophie ^[4] ; Rafat, Cedric ^[5] ; Letavernier, Emmanuel ^[6] ; Tillet, Yves ^[7] ; Rondeau, Eric ^[8] ; Leite-de-Moraes, Maria C. ^[9]

Afiliação do(s) autor(es)

^[1] Hop Tenon. INSERM

^[2] Univ Paris 05. Fac Med

^[3] Univ Paris 05. Fac Med

^[4] Hop Tenon. INSERM

^[5] Hop Tenon. INSERM

^[6] Hop Tenon. INSERM

^[7] INRA. UMR85

^[8] Hop Tenon. INSERM

^[9] Univ Paris 05. Fac Med

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; v. 20, n. 6, p. 1282-1292, JUN 2009.
• Citações Web of Science: 35

Resumo

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. (AU)

• Processo FAPESP: 07/07120-0 - O papel de células T invariantes natural killer no desenvolvimento de glomerulonefrite: mecanismos e perspectivas
• Beneficiário: Alexandre de Castro Keller
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores