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Immunity. 2018 Feb 20;48(2):286-298.e6. doi: 10.1016/j.immuni.2018.01.004. Epub 2018 Jan 27.

Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR4.

Author information

1
Laboratory of Immune Regulation, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan; Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
2
Laboratory of Immune Regulation, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
3
Laboratory of Immune Regulation, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan; Laboratory of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
4
Reproductive Engineering Team, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
5
Division of Host Defense, Network Center for Infectious Diseases, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
6
Laboratory of Stem Cell Biology and Developmental Immunology, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
7
Department of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg 69120, Germany.
8
Laboratory of Immune Regulation, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. Electronic address: ikuta.koichi.6c@kyoto-u.ac.jp.

Abstract

Glucocorticoids are steroid hormones with strong anti-inflammatory and immunosuppressive effects that are produced in a diurnal fashion. Although glucocorticoids have the potential to induce interleukin-7 receptor (IL-7R) expression in T cells, whether they control T cell homeostasis and responses at physiological concentrations remains unclear. We found that glucocorticoid receptor signaling induces IL-7R expression in mouse T cells by binding to an enhancer of the IL-7Rα locus, with a peak at midnight and a trough at midday. This diurnal induction of IL-7R supported the survival of T cells and their redistribution between lymph nodes, spleen, and blood by controlling expression of the chemokine receptor CXCR4. In mice, T cell accumulation in the spleen at night enhanced immune responses against soluble antigens and systemic bacterial infection. Our results reveal the immunoenhancing role of glucocorticoids in adaptive immunity and provide insight into how immune function is regulated by the diurnal rhythm.

KEYWORDS:

CXCR4; T cell; diurnal rhythm; glucocorticoid; interleukin-7

PMID:
29396162
DOI:
10.1016/j.immuni.2018.01.004
[Indexed for MEDLINE]
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