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
Affiliations
Qingyang Liu
Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA; Mary H. Weiser Food Allergy Center, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA; Immunology Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA
Shams Tabrez
Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA; Mary H. Weiser Food Allergy Center, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
Patrick Niekamp
Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA; Mary H. Weiser Food Allergy Center, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA
Chang H. Kim
Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA; Mary H. Weiser Food Allergy Center, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA; Immunology Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA; Rogel Cancer Center, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA; Corresponding author
Summary: 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 (BM) ILCPs.
