Inhibition of CD1d-mediated antigen presentation by the transforming growth factor-beta/Smad signalling pathway

摘要

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-) 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- in the activation of p38. Therefore, we hypothesized that TGF- 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- treatment. However, it was found that this inhibition was not through p38 activation. Instead, Smads 2, 3 and 4, downstream elements of the TGF- canonical signalling pathway, contributed to the observed effects. In marked contrast to that observed with CD1d, TGF- was found to enhance MHC class II-mediated antigen presentation. Overall, these results suggest that the canonical TGF-/Smad pathway negatively regulates an important arm of the host's innate immune responses-CD1d-mediated lipid antigen presentation to NKT cells.