TY - JOUR
T1 - Glucocorticoids Drive Diurnal Oscillations in T Cell Distribution and Responses by Inducing Interleukin-7 Receptor and CXCR4
AU - Shimba, Akihiro
AU - Cui, Guangwei
AU - Tani-ichi, Shizue
AU - Ogawa, Makoto
AU - Abe, Shinya
AU - Okazaki, Fumie
AU - Kitano, Satsuki
AU - Miyachi, Hitoshi
AU - Yamada, Hisakata
AU - Hara, Takahiro
AU - Yoshikai, Yasunobu
AU - Nagasawa, Takashi
AU - Schütz, Günther
AU - Ikuta, Koichi
N1 - Funding Information:
We would like to acknowledge Drs. J. Takeda, K. Yusa, and G. Kondoh for providing the KY1.1 ES line and targeting system and Dr. Batu Erman and members of the K. Ikuta laboratory for discussion. This work was supported by JSPS KAKENHI grant numbers 16K15288 , 16H05172 , and 15H01153 (K.I.), 26460572 (S.T.), and 16K08835 (T.H.), by the Joint Usage/Research Center program of Institute for Frontier Life and Medical Sciences Kyoto University , by the Future Developmental Funding Program of Kyoto University Research Coordination Alliance , and by the Japan Society for the Promotion of Science (JSPS) and TUBITAK Joint Research Project . A.S. was supported by the Platform for Dynamic Approaches to Living System from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) and Japan Agency for Medical Research and Development (AMED) . G.C. was an International Research Fellow of the Japan Society for the Promotion of Science .
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/2/20
Y1 - 2018/2/20
N2 - 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.
AB - 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.
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U2 - 10.1016/j.immuni.2018.01.004
DO - 10.1016/j.immuni.2018.01.004
M3 - Article
C2 - 29396162
AN - SCOPUS:85040997477
VL - 48
SP - 286-298.e6
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 2
ER -
