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Circadian-clock-controlled endocrine and cytokine signals regulate multipotential innate lymphoid cell progenitors in the bone marrow.

Qingyang Liu | Shams Tabrez | Patrick Niekamp | Chang H Kim
Cell reports | 2024

Innate lymphoid cells (ILCs), strategically positioned throughout the body, undergo population declines over time. A solution to counteract this problem is timely mobilization of multipotential progenitors from the bone marrow. It remains unknown what triggers the mobilization of bone marrow ILC progenitors (ILCPs). We report that ILCPs are regulated by the circadian clock to emigrate and generate mature ILCs in the periphery. We found that circadian-clock-defective ILCPs fail to normally emigrate and generate ILCs. We identified circadian-clock-controlled endocrine and cytokine cues that, respectively, regulate the retention and emigration of ILCPs at distinct times of each day. Activation of the stress-hormone-sensing glucocorticoid receptor upregulates CXCR4 on ILCPs for their retention in the bone marrow, while the interleukin-18 (IL-18) and RORα signals upregulate S1PR1 on ILCPs for their mobilization to the periphery. Our findings establish important roles of circadian signals for the homeostatic efflux of bone marrow ILCPs.

Pubmed ID: 38717905 RIS Download

Antibodies used in this publication

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P30 CA046592
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI121302
  • Agency: NIAID NIH HHS, United States
    Id: R56 AI173179
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI173179
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI148898

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