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.
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Authors | Laurent Mesnard, Alexandre C Keller, Marie-Laure Michel, Sophie Vandermeersch, Cédric Rafat, Emmanuel Letavernier, Yves Tillet, Eric Rondeau, Maria C Leite-de-Moraes |
Journal | Journal of the American Society of Nephrology : JASN
(J Am Soc Nephrol)
Vol. 20
Issue 6
Pg. 1282-92
(Jun 2009)
ISSN: 1533-3450 [Electronic] United States |
PMID | 19470687
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Extracellular Matrix Proteins
- Transforming Growth Factor beta
- betaIG-H3 protein
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Topics |
- Animals
- Anti-Glomerular Basement Membrane Disease
(immunology, metabolism)
- Antibodies, Monoclonal
- Extracellular Matrix Proteins
(metabolism)
- Kidney
(pathology)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Natural Killer T-Cells
(physiology)
- T-Lymphocytes, Helper-Inducer
(metabolism)
- Transforming Growth Factor beta
(immunology, metabolism)
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