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" Inhibition of IRF4 in dendritic cells by PRR-independent and -dependent signals inhibit Th2 and promote Th17 responses. "
Lee, JihyungZhang, JunyanChung, Young-JunKim, Jun HwanKook, Chae MinGonzález-Navajas, José MHerdman, David SNürnberg, BerndInsel, Paul ACorr, MaripatMo, Ji-HunTao, AilinYasuda, KeiRifkin, Ian RBroide, David HSciammas, RogerWebster, Nicholas JgRaz, Eyal
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AL
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| Record Number
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902575
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LA36t0j6gq
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| Title & Author
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Inhibition of IRF4 in dendritic cells by PRR-independent and -dependent signals inhibit Th2 and promote Th17 responses. [Article]\ Lee, JihyungZhang, JunyanChung, Young-JunKim, Jun HwanKook, Chae MinGonzález-Navajas, José MHerdman, David SNürnberg, BerndInsel, Paul ACorr, MaripatMo, Ji-HunTao, AilinYasuda, KeiRifkin, Ian RBroide, David HSciammas, RogerWebster, Nicholas JgRaz, Eyal
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2020
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| Title of Periodical
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UC San Diego
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| Abstract
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Cyclic AMP (cAMP) is involved in many biological processes but little is known regarding its role in shaping immunity. Here we show that cAMP-PKA-CREB signaling (a pattern recognition receptor [PRR]-independent mechanism) regulates conventional type-2 Dendritic Cells (cDC2s) in mice and reprograms their Th17-inducing properties via repression of IRF4 and KLF4, transcription factors essential for cDC2-mediated Th2 induction. In mice, genetic loss of IRF4 phenocopies the effects of cAMP on Th17 induction and restoration of IRF4 prevents the cAMP effect. Moreover, curdlan, a PRR-dependent microbial product, activates CREB and represses IRF4 and KLF4, resulting in a pro-Th17 phenotype of cDC2s. These in vitro and in vivo results define a novel signaling pathway by which cDC2s display plasticity and provide a new molecular basis for the classification of novel cDC2 and cDC17 subsets. The findings also reveal that repressing IRF4 and KLF4 pathway can be harnessed for immuno-regulation.
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