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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chemokine CXCL12 / biosynthesis
  • Circadian Rhythm / physiology*
  • Female
  • Glucocorticoids / pharmacology*
  • Immunologic Memory
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Receptors, CXCR4 / physiology*
  • Receptors, Glucocorticoid / physiology
  • Receptors, Interleukin-7 / physiology*
  • T-Lymphocytes / immunology*

Substances

  • CXCR4 protein, mouse
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Glucocorticoids
  • Receptors, CXCR4
  • Receptors, Glucocorticoid
  • Receptors, Interleukin-7