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Invariant natural killer T cells and TGF-beta attenuate anti-GBM glomerulonephritis.


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 (Jalpha18-/-) 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 Jalpha18-/- mice. Interestingly, expression of both TGF-beta and TGF-beta-induced (TGFBI) mRNA was higher in wild-type kidneys compared with Jalpha18-/- 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 Jalpha18-/-, mice. In conclusion, in experimental anti-GBM GN, iNKT cells attenuate disease severity and TGF-beta has a renoprotective role.

SUBMITTER: Mesnard L 

PROVIDER: S-EPMC2689902 | biostudies-other | 2009 Jun

REPOSITORIES: biostudies-other

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Invariant natural killer T cells and TGF-beta attenuate anti-GBM glomerulonephritis.

Mesnard Laurent L   Keller Alexandre C AC   Michel Marie-Laure ML   Vandermeersch Sophie S   Rafat Cédric C   Letavernier Emmanuel E   Tillet Yves Y   Rondeau Eric E   Leite-de-Moraes Maria C MC  

Journal of the American Society of Nephrology : JASN 20090521 6


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 (Jalpha1  ...[more]

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