Institute for Frontier Life and Medical Sciences, Kyoto University

Glucocorticoids drive diurnal oscillations in T cell distribution and responses by inducing interleukin-7 receptor and CXCR4

Akihiro Shimba1,2, Guangwei Cui1, Shizue Tani-ichi1,3, Makoto Ogawa1,2, Shinya Abe1,2, Fumie Okazaki1,2, Satsuki Kitano4, Hitoshi Miyachi4, Hisataka Yamada5, Takahiro Hara1, Yasunobu Yoshikai5, Takashi Nagasawa6, Günther Schütz7, and Koichi Ikuta1

(1Laboratory of Immune Regulation, Institute for Frontier Life and Medical Sciences, Kyoto University; 2Graduate School of Medicine, Kyoto University; 3Laboratory of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University; 4Reproductive Engineering Team, Institute for Frontier Life and Medical Sciences, Kyoto University; 5Medical Institute of Bioregulation, Kyushu University; 6Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University; 7German Cancer Research Center)

Immunity (2018) in press. doi: 10.1016/j.immuni.2018.01.004

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-7R 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.

Figure. Glucocorticoids drive diurnal oscillations in T cell distribution and responses by inducing interleukin-7 receptor and CXCR4