Invariant natural killer T cells and TGF-beta attenuate anti-GBM glomerulonephritis.
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.
Mesnard
Laurent
L
INSERM, UMR S 702, Hôpital Tenon, Paris, France.
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
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology* / Q000378:metabolism; D000911:Antibodies, Monoclonal; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D007668:Kidney / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*; D000099222:betaIG-H3 Protein
D000911:Antibodies, Monoclonal; D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein