English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

IL-17-producing CD4 T cells play a key role in immune responses against extracellular bacteria and autoimmunity. Nuclear factor κB (NF-κB) is required for T-cell activation and selected effector functions, but its role in Th17 differentiation is controversial. Using genetic mouse models that impede T-cell-NF-κB signaling either downstream of the T-cell receptor (TCR) or of IκB kinase β (IKKβ), we demonstrate that NF-κB signaling controls not only survival and proliferation of activated T cells, but, if cell survival and cell-cycle progression are enabled, has an additional role in promoting completion of Th17 differentiation. CARD-containing MAGUK protein 1 (CARMA1), an adapter required for TCR/NF-κB signaling, was necessary for acquisition of IL-17A, IL-17F, IL-21, IL-22, IL-23R, and CCR6 expression in T cells cultured under Th17 conditions. In proliferating cells, lack of CARMA1 selectively prevented Th17, but not Th1 or Th2 differentiation, in a cell-intrinsic manner. Consistent with these data, CARMA1-KO mice were resistant to experimental autoimmune encephalomyelitis. Surprisingly, transcription factors essential for Th17 differentiation such as RORγt, AHR, and IRF4 were normally induced in CARMA1-KO T cells activated under Th17 conditions, suggesting that the Th17 differentiation program was initiated normally. Instead, chromatin loci of Th17 effector molecules failed to acquire an open conformation in CARMA1-KO T cells. Our results demonstrate that TCR/CARMA1/NF-κB controls completion of Th17 differentiation by enabling chromatin accessibility of Th17 effector molecule loci.

T cell receptor/CARMA1/NF-κB signaling controls T-helper (Th) 17 differentiation