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Szabo, A; Bene, K; Gogolak, P; Rethi, B; Lanyi, A; Jankovich, I; Dezso, B; Rajnavolgyi, E
Journal of leukocyte biology, July 2012, Letnik: 92, Številka: 1Journal Article
Identification of the CD1a+ moDC as an inflammatory subset with specialized activation of RLR and associated cytokine and functional activities. 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+PPARγlowCD1a+ and CD14lowDC‐SIGN+PPARγhighCD1a− 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‐β via IRF3, whereas induction of proinflammatory cytokine responses were predominantly controlled by TLR3. The requirement of RLR‐mediated signaling in CD1a+ moDCs for priming naïve 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.
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Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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