TH17 cell differentiation is regulated by the circadian clock

Xiaofei Yu, Darcy Rollins, Kelly A. Ruhn, Jeremy J. Stubblefield, Carla B. Green, Masaki Kashiwada, Paul B. Rothman, Joseph S. Takahashi, Lora V. Hooper

Research output: Contribution to journalArticle

181 Scopus citations

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 (TH17) 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 TH17 cell development by directly binding and repressing the Rorgt promoter. NFIL3 links TH17 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 TH17 cell frequencies and increased susceptibility to inflammatory disease. Thus, lineage specification of a key immune cell is under direct circadian control.

Original languageEnglish (US)
Pages (from-to)727-730
Number of pages4
JournalScience
Volume342
Issue number6159
DOIs
StatePublished - Jan 1 2013

ASJC Scopus subject areas

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    Yu, X., Rollins, D., Ruhn, K. A., Stubblefield, J. J., Green, C. B., Kashiwada, M., Rothman, P. B., Takahashi, J. S., & Hooper, L. V. (2013). TH17 cell differentiation is regulated by the circadian clock. Science, 342(6159), 727-730. https://doi.org/10.1126/science.1243884