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

Akihiro Shimba, Guangwei Cui, Shizue Tani-ichi, Makoto Ogawa, Shinya Abe, Fumie Okazaki, Satsuki Kitano, Hitoshi Miyachi, Hisakata Yamada, Takahiro Hara, Yasunobu Yoshikai, Takashi Nagasawa, Günther Schütz, Koichi Ikuta

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    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. Glucocorticoids have strong immunosuppressive effects, yet their physiological functions in the immune system remain unclear. Shimba et al. demonstrate that glucocorticoids drive IL-7R expression in a diurnal fashion, which induces the redistribution of T cells between peripheral blood and lymphoid organs via CXCR4 expression and enhances adaptive immune responses.

    Original languageEnglish
    Pages (from-to)286-298.e6
    JournalImmunity
    Volume48
    Issue number2
    DOIs
    Publication statusPublished - Feb 20 2018

    Fingerprint

    Interleukin-7 Receptors
    Glucocorticoids
    T-Lymphocytes
    Adaptive Immunity
    Immunosuppressive Agents
    Spleen
    Chemokine Receptors
    Glucocorticoid Receptors
    Circadian Rhythm
    Bacterial Infections
    Immune System
    Homeostasis
    Anti-Inflammatory Agents
    Lymph Nodes
    Steroids
    Hormones
    Antigens

    All Science Journal Classification (ASJC) codes

    • Immunology and Allergy
    • Immunology
    • Infectious Diseases

    Cite this

    Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR4. / Shimba, Akihiro; Cui, Guangwei; Tani-ichi, Shizue; Ogawa, Makoto; Abe, Shinya; Okazaki, Fumie; Kitano, Satsuki; Miyachi, Hitoshi; Yamada, Hisakata; Hara, Takahiro; Yoshikai, Yasunobu; Nagasawa, Takashi; Schütz, Günther; Ikuta, Koichi.

    In: Immunity, Vol. 48, No. 2, 20.02.2018, p. 286-298.e6.

    Research output: Contribution to journalArticle

    Shimba, A, Cui, G, Tani-ichi, S, Ogawa, M, Abe, S, Okazaki, F, Kitano, S, Miyachi, H, Yamada, H, Hara, T, Yoshikai, Y, Nagasawa, T, Schütz, G & Ikuta, K 2018, 'Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR4', Immunity, vol. 48, no. 2, pp. 286-298.e6. https://doi.org/10.1016/j.immuni.2018.01.004
    Shimba, Akihiro ; Cui, Guangwei ; Tani-ichi, Shizue ; Ogawa, Makoto ; Abe, Shinya ; Okazaki, Fumie ; Kitano, Satsuki ; Miyachi, Hitoshi ; Yamada, Hisakata ; Hara, Takahiro ; Yoshikai, Yasunobu ; Nagasawa, Takashi ; Schütz, Günther ; Ikuta, Koichi. / Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR4. In: Immunity. 2018 ; Vol. 48, No. 2. pp. 286-298.e6.
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