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Inhibition of CD 1d‐mediated antigen presentation by the transforming growth factor‐ β /Smad signalling pathway
Author(s) -
Bailey Jennifer C.,
Iyer Abhirami K.,
Renukaradhya Gourapura J.,
Lin Yinling,
Nguyen Hoa,
Brutkiewicz Randy R.
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12353
Subject(s) - cd1d , antigen presentation , antigen processing , biology , microbiology and biotechnology , smad , antigen , immune system , innate immune system , immunology , natural killer t cell , transforming growth factor , t cell
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.