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The Cell-Intrinsic Circadian Clock Is Dispensable for Lymphocyte Differentiation and Function.
Hemmers, Saskia; Rudensky, Alexander Y.
Affiliation
  • Hemmers S; Immunology Program and Ludwig Center, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Rudensky AY; Immunology Program and Ludwig Center, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: rudenska@mskcc.org.
Cell Rep ; 11(9): 1339-49, 2015 Jun 09.
Article in En | MEDLINE | ID: mdl-26004187
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.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: B-Lymphocytes / T-Lymphocytes / Cell Differentiation / Circadian Clocks Limits: Animals Language: En Journal: Cell Rep Year: 2015 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: B-Lymphocytes / T-Lymphocytes / Cell Differentiation / Circadian Clocks Limits: Animals Language: En Journal: Cell Rep Year: 2015 Type: Article