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

• Published in: Cell reports (Cambridge) 2015-06, Vol.11 (9), p.1339-1349
• Main Authors: Hemmers, Saskia, Rudensky, Alexander Y.
• Format: Article
• Language: English
• Subjects: Animals; ARNTL Transcription Factors - deficiency; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Cell Differentiation - immunology; Circadian Clocks - immunology; Flow Cytometry; Mice; Mice, Knockout; Polymerase Chain Reaction; T-Lymphocytes - cytology; T-Lymphocytes - immunology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2015.04.058

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. [Display omitted] •The cell-intrinsic circadian clock is dispensable for T- and B-cell development•TH17 differentiation is normal in mice with a T-cell-specific deletion of Bmal1•Circadian gating of IL-2 secretion is independent of the cell-intrinsic clock The circadian clock regulates a multitude of processes, including behavior, metabolism, and immunity. Hemmers and Rudensky investigate the cell-intrinsic requirement for a circadian clock in adaptive immunity. Lymphocyte-specific deletion of Bmal1 revealed that the circadian clock is dispensable for normal differentiation and function.