Format

Send to

Choose Destination
See comment in PubMed Commons below
Science. 2013 Nov 8;342(6159):727-30. doi: 10.1126/science.1243884.

TH17 cell differentiation is regulated by the circadian clock.

Author information

  • 1Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Abstract

Circadian clocks regulate numerous physiological processes that vary across the day-night (diurnal) cycle, but if and how the circadian clock regulates the adaptive immune system is mostly unclear. Interleukin-17-producing CD4(+) T helper (T(H)17) cells are proinflammatory immune cells that protect against bacterial and fungal infections at mucosal surfaces. Their lineage specification is regulated by the orphan nuclear receptor RORγt. We show that the transcription factor NFIL3 suppresses T(H)17 cell development by directly binding and repressing the Rorγt promoter. NFIL3 links T(H)17 cell development to the circadian clock network through the transcription factor REV-ERBα. Accordingly, TH17 lineage specification varies diurnally and is altered in Rev-erbα(-/-) mice. Light-cycle disruption elevated intestinal T(H)17 cell frequencies and increased susceptibility to inflammatory disease. Thus, lineage specification of a key immune cell is under direct circadian control.

PMID:
24202171
PMCID:
PMC4165400
DOI:
10.1126/science.1243884
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center