Invariant Natural Killer T (iNKT) cells represent a particular subset of T lymphocytes capable of promptly producing several cytokines following TCR stimulation, through which they can exert regulatory or effector functions, depending on the immunological context.

Invariant NKT cell-deficient mice (Ja18^-/-) were compared to their Wild Type (WT) counterpart. They were challenged by nephrotoxic serum injection without pre-immunisation. Kidney mononuclear cells were separated by gradient centrifugation for FACS analysis to determined iNKT renal infiltration. Immunohistological analysis of glomerular aggressions (Crescents), BUN and proteinuria were also performed. TGF-β1, TGF-β1-induced gene (TGFBI) mRNA were analysed using RT-PCR from renal cortex extracts. Serum and kidney extract level of TGF-b1 protein were determined . TGF-b1 activity was blocked by the in vivo administration of an anti-TGF-β neutralizing antibody (1D11) during initial course of the nephritis.

We observed a rapid increase in the number of kidney iNKT cells after anti-GBM serum injection. The analysis of Ja18^-/- mice injected with anti-GBM serum clearly demonstrated higher levels of BUN and proteinuria associated with greater glomerular and tubular injury in comparison to WT animals. We did not detect any significant differences concerning Th1/Th2 polarization in renal tissue that might have explained the severity of the disease observed in Ja18^-/- mice. The expression of both TGF-b and TGFBI mRNA was more elevated in the kidneys of WT animals as compared to Ja18^-/- animals, suggesting a possible role for TGF-b in the control of anti-GBM GN. In support of this idea, we found that in vivo administration of an anti-TGF-β neutralizing antibody significantly enhanced the severity of the disease in WT but not Ja18^-/- mice.

Our results suggest that iNKT cells may attenuate auto- or alloimmune-mediated renal injury. We found a striking relationship between iNKT cell deficiency and impaired production of TGF-b. Unlike previous studies that describe the harmful role of TGF-b during the development of renal fibrosis or nephritis, herein, we have demonstrated that the absence of TGF-b exacerbates the loss of renal function and the influx of inflammatory cells.

Our findings demonstrated a new reno-protective role for TGF-b in experimental anti-GBM GN. Moreover, our data indicate that both iNKT cells and TGF-β are required in the regulation of acute glomerular injury.