title: Inhibition of CD1d-mediated antigen presentation by the transforming growth factor-β/Smad signalling pathway.
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.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Bailey
authors.forename: Abhirami K
authors.initials: AK
authors.lastname: Iyer
authors.forename: Gourapura J
authors.initials: GJ
authors.lastname: Renukaradhya
authors.forename: Yinling
authors.initials: Y
authors.lastname: Lin
authors.forename: Hoa
authors.initials: H
authors.lastname: Nguyen
authors.forename: Randy R
authors.initials: RR
authors.lastname: Brutkiewicz
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D055610:Antigens, CD1d / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008055:Lipids / Q000276:immunology; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D018448:Models, Immunological; D021381:Protein Transport; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D055610:Antigens, CD1d; D000949:Histocompatibility Antigens Class II; D008055:Lipids; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D048051:p38 Mitogen-Activated Protein Kinases
keywords: antigen presentation/processing; rodent; signal transduction