عنوان

Inhibition of IRF4 in dendritic cells by PRR-independent and -dependent signals inhibit Th2 and promote Th17 responses.

Number

LA36t0j6gq

Title Proper

Inhibition of IRF4 in dendritic cells by PRR-independent and -dependent signals inhibit Th2 and promote Th17 responses.

General Material Designation

[Article]

First Statement of Responsibility

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

Text of Note

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.

Date of Publication

2020

Title

UC San Diego

Electronic name

[Article]

278925

a

Y