期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 92, 期 1, 页码 159-169出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.0711360
关键词
innate immunity; RIG-I-like receptor; inflammatory cytokine; influenza
资金
- Hungarian Scientific Research [OTKA NK-72937, NK-101538, TAMOP 4.2.1./B-09/1/KONV-2010-0007]
Cytosolic RIG-I-like helicases (RLR) are PRRs involved in type I IFN production and antiviral immunity. This study focuses to the comparison of the expression, function, and signaling cascades associated to RLR in the previously identified CD14(-)DC-SIGN(+)PPAR gamma(low)CD1a(+) and CD14(low)DC-SIGN(+)PPAR gamma(high)CD1a(-) human moDC subsets. Our results revealed that the expression of RLR genes and proteins as well as the activity of the coupled signaling pathways are significantly higher in the CD1a(+) subset than in its phenotypically and functionally distinct counterpart. Specific activation of RLR in moDCs by poly(I: C) or influenza virus was shown to induce the secretion of IFN-beta via IRF3, whereas induction of proinflammatory cytokine responses were predominantly controlled by TLR3. The requirement of RLR-mediated signaling in CD1a(+) moDCs for priming naive CD8(+) T lymphocytes and inducing influenza virus-specific cellular immune responses was confirmed by RIG-I/MDA5 silencing, which abrogated these functions. Our results demonstrate the subset-specific activation of RLR and the underlying mechanisms behind its cytokine secretion profile and identify CD1a(+) moDCs as an inflammatory subset with specialized functional activities. We also provide evidence that this migratory DC subset can be detected in human tonsil and reactive LNs. J. Leukoc. Biol. 92: 159-169; 2012.
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