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

被引：137

作者：

Shimba, Akihiro ^{[1
,2
]}

Cui, Guangwei ^{[1
]}

Tani-ichi, Shizue ^{[1
,3
]}

Ogawa, Makoto ^{[1
,2
]}

Abe, Shinya ^{[1
,2
]}

Okazaki, Fumie ^{[1
,2
]}

Kitano, Satsuki ^{[4
]}

Miyachi, Hitoshi ^{[4
]}

Yamada, Hisakata ^{[5
]}

Hara, Takahiro ^{[1
]}

Yoshikai, Yasunobu ^{[5
]}

Nagasawa, Takashi ^{[6
,7
]}

Schuetz, Gunther ^{[8
]}

Ikuta, Koichi ^{[1
]}

机构：

[1] Kyoto Univ, Inst Frontier Life & Med Sci, Dept Virus Res, Lab Immune Regulat, Kyoto 6068507, Japan

[2] Kyoto Univ, Grad Sch Med, Kyoto 6068501, Japan

[3] Kyoto Univ, Grad Sch Med, Lab Biol Chem, Human Hlth Sci, Kyoto 6068507, Japan

[4] Kyoto Univ, Inst Frontier Life & Med Sci, Reprod Engn Team, Kyoto 6068507, Japan

[5] Kyushu Univ, Network Ctr Infect Dis, Med Inst Bioregulat, Div Host Def, Fukuoka 8128582, Japan

[6] Osaka Univ, Grad Sch Frontier Biosci, Lab Stem Cell Biol & Dev Immunol, Osaka 5650871, Japan

[7] Osaka Univ, Grad Sch Med, Osaka 5650871, Japan

[8] German Canc Res Ctr, Dept Mol Biol Cell 1, D-69120 Heidelberg, Germany

来源：

IMMUNITY | 2018年 / 48卷 / 02期

基金：

日本学术振兴会;

关键词：

CIRCADIAN CLOCK; IN-VIVO; IL-7; RECEPTOR; THYMOCYTE SUBPOPULATIONS; IMMUNE-RESPONSE; EXPRESSION; HOMEOSTASIS; ACTIVATION; INHIBITION; DIFFERENTIATION;

D O I：

10.1016/j.immuni.2018.01.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 inter-leukin-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 alpha 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.

引用

页码：286 / +

页数：19

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