| First Author | Bailey JC | Year | 2014 |
| Journal | Immunology | Volume | 143 |
| Issue | 4 | Pages | 679-91 |
| PubMed ID | 24990409 | Mgi Jnum | J:220145 |
| Mgi Id | MGI:5632282 | Doi | 10.1111/imm.12353 |
| Citation | Bailey JC, et al. (2014) Inhibition of CD1d-mediated antigen presentation by the transforming growth factor-beta/Smad signalling pathway. Immunology 143(4):679-91 |
| abstractText | 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-beta) 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-beta in the activation of p38. Therefore, we hypothesized that TGF-beta 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-beta treatment. However, it was found that this inhibition was not through p38 activation. Instead, Smads 2, 3 and 4, downstream elements of the TGF-beta canonical signalling pathway, contributed to the observed effects. In marked contrast to that observed with CD1d, TGF-beta was found to enhance MHC class II-mediated antigen presentation. Overall, these results suggest that the canonical TGF-beta/Smad pathway negatively regulates an important arm of the host's innate immune responses - CD1d-mediated lipid antigen presentation to NKT cells. |
