In:
The Journal of Immunology, The American Association of Immunologists, Vol. 192, No. 1_Supplement ( 2014-05-01), p. 111.14-111.14
Abstract:
CD1d is a MHC class I-like molecule that presents lipid Ags to a subpopulation of innate lymphocytes called natural killer T cells. In a prior study, we showed that the mitogen-activated protein kinase p38 is a negative regulator of Ag presentation by CD1d. It is unknown how p38 is activated to induce this regulation; however, several studies have implicated a role for the immunoregulatory cytokine, TGF-β, in the activation of p38. Therefore, we hypothesized that TGF-β negatively regulates the CD1d-mediated Ag presentation pathway. Indeed, a dose-dependent decrease in CD1d-mediated Ag presentation and impairment of lipid Ag processing was observed in TGF-β-treated antigen presenting cells. However, this inhibition was not through p38 activation. Instead, by employing a lentiviral shRNA-based approach, we found that the canonical TGF-β signaling elements, Smads 2, 3 and 4, contributed to the TGF-β-mediated inhibition of Ag presentation by CD1d. Furthermore, a side-by-side comparative analysis of the effect of TGF-β on CD1d and MHC class II-mediated Ag presentation revealed that in contrast to that observed with CD1d, TGF-β actually enhances MHC class II-mediated Ag presentation. Overall, these results suggest that the canonical TGF-β/Smad pathway has distinctly different effects on the regulation of CD1d- and MHC class II-mediated antigen presentation pathways.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.192.Supp.111.14
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2014
detail.hit.zdb_id:
1475085-5
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