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

Jennifer C. Bailey, Abhirami K. Iyer, Gourapura J. Renukaradhya, Yinling Lin, Hoa Nguyen, Randy R. Brutkiewicz

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish
Pages (from-to)679-691
Number of pages13
Issue number4
StatePublished - Dec 1 2014


  • Antigen presentation/processing
  • Rodent
  • Signal transduction


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