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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.
AuthorsLaurent Mesnard, Alexandre C Keller, Marie-Laure Michel, Sophie Vandermeersch, Cédric Rafat, Emmanuel Letavernier, Yves Tillet, Eric Rondeau, Maria C Leite-de-Moraes
JournalJournal 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
PMID19470687 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Extracellular Matrix Proteins
  • Transforming Growth Factor beta
  • betaIG-H3 protein
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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