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 Brutkiewicz

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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
JournalImmunology
Volume143
Issue number4
DOIs
StatePublished - Dec 1 2014

Fingerprint

CD1d Antigen
Antigen Presentation
Transforming Growth Factors
Natural Killer T-Cells
Lipids
Histocompatibility Antigens Class II
p38 Mitogen-Activated Protein Kinases
Innate Immunity
Immune System
Lymphocytes
Cytokines

Keywords

  • Antigen presentation/processing
  • Rodent
  • Signal transduction

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Inhibition of CD1d-mediated antigen presentation by the transforming growth factor-β/Smad signalling pathway. / Bailey, Jennifer C.; Iyer, Abhirami K.; Renukaradhya, Gourapura J.; Lin, Yinling; Nguyen, Hoa; Brutkiewicz, Randy.

In: Immunology, Vol. 143, No. 4, 01.12.2014, p. 679-691.

Research output: Contribution to journalArticle

Bailey, Jennifer C. ; Iyer, Abhirami K. ; Renukaradhya, Gourapura J. ; Lin, Yinling ; Nguyen, Hoa ; Brutkiewicz, Randy. / Inhibition of CD1d-mediated antigen presentation by the transforming growth factor-β/Smad signalling pathway. In: Immunology. 2014 ; Vol. 143, No. 4. pp. 679-691.
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