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Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Immunology 2014 ; 143 (4): 679-91 Nephropedia Template TP
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Inhibition of CD1d-mediated antigen presentation by the transforming growth factor-?/Smad signalling pathway #MMPMID24990409
Immunology 2014[Dec]; 143 (4): 679-91 PMID24990409show ga
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.