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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 9
Affiliation:
[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
Total Affiliations: 9
Document type: Journal article
Source: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; v. 20, n. 6, p. 1282-1292, JUN 2009.
Web of Science Citations: 35
Abstract

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)

FAPESP's process: 07/07120-0 - The role of invariant natural killer T cells in the development of glomerulonephritis: mechanisms and perspectives
Grantee:Alexandre de Castro Keller
Support Opportunities: Research Grants - Young Investigators Grants