Inhibition of CD 1d‐mediated antigen presentation by the transforming growth factor‐ β /Smad signalling pathway

Summary CD1d‐mediated lipid antigen presentation activates a subset of innate immune lymphocytes called invariant natural killer T ( NKT ) cells that, by virtue of their potent cytokine production, bridge the innate and adaptive immune systems. Transforming growth factor (TGF‐ β ) is a known immune modulator that can activate the mitogen‐activated protein kinase p38; we have previously shown that p38 is a negative regulator of CD1d‐mediated antigen presentation. Several studies implicate a role for TGF‐ β in the activation of p38. Therefore, we hypothesized that TGF‐ β would impair antigen presentation by CD1d. Indeed, a dose‐dependent decrease in CD1d‐mediated antigen presentation and impairment of lipid antigen processing was observed in response to TGF‐ β treatment. However, it was found that this inhibition was not through p38 activation. Instead, Smads 2, 3 and 4, downstream elements of the TGF‐ β canonical signalling pathway, contributed to the observed effects. In marked contrast to that observed with CD1d, TGF‐ β was found to enhance MHC class II‐mediated antigen presentation. Overall, these results suggest that the canonical TGF‐ β /Smad pathway negatively regulates an important arm of the host's innate immune responses – CD1d‐mediated lipid antigen presentation to NKT cells.