The Cell-Intrinsic Circadian Clock Is Dispensable for Lymphocyte Differentiation and Function.

Journal Article (Journal Article)

Circadian rhythms regulate many aspects of physiology, ranging from sleep-wake cycles and metabolic parameters to susceptibility to infection. The molecular clock, with transcription factor BMAL1 at its core, controls both central and cell-intrinsic circadian rhythms. Using a circadian reporter, we observed dynamic regulation of clock activity in lymphocytes. However, its disruption upon conditional Bmal1 ablation did not alter T- or B-cell differentiation or function. Although the magnitude of interleukin 2 (IL-2) production was affected by the time of bacterial infection, it was independent of cell-intrinsic expression of BMAL1. The circadian gating of the IL-2 response was preserved in Bmal1-deficient T cells, despite a slight reduction in cytokine production in a competitive setting. Our results suggest that, contrary to the prevailing view, the adaptive immune response is not affected by the cell-intrinsic clock but is likely influenced by cell-extrinsic circadian cues operating across multiple cell types.

Full Text

Duke Authors

Cited Authors

  • Hemmers, S; Rudensky, AY

Published Date

  • June 9, 2015

Published In

Volume / Issue

  • 11 / 9

Start / End Page

  • 1339 - 1349

PubMed ID

  • 26004187

Pubmed Central ID

  • PMC4464971

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2015.04.058


  • eng

Conference Location

  • United States