Interleukin-22 Drives Endogenous Thymic Regeneration in Mice

被引：297

作者：

Dudakov, Jarrod A. ^{[1
,2
]}

Hanash, Alan M. ^{[3
]}

Jenq, Robert R. ^{[3
,4
]}

Young, Lauren F. ^{[1
]}

Ghosh, Arnab ^{[1
]}

Singer, Natalie V. ^{[1
]}

West, Mallory L. ^{[1
]}

Smith, Odette M. ^{[1
]}

Holland, Amanda M. ^{[1
,5
]}

Tsai, Jennifer J. ^{[1
,5
]}

Boyd, Richard L. ^{[2
]}

van den Brink, Marcel R. M. ^{[1
,3
,4
,5
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10065 USA

[2] Monash Univ, Monash Immunol & Stem Cell Labs, Melbourne, Vic 3800, Australia

[3] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

[4] Weill Cornell Med Coll, Dept Med, New York, NY 10021 USA

[5] Weill Cornell Med Coll, Dept Immunol & Microbial Pathogenesis, New York, NY 10021 USA

来源：

SCIENCE | 2012年 / 336卷 / 6077期

基金：

英国医学研究理事会;

关键词：

INNATE LYMPHOID-CELLS; ROR-GAMMA-T; EPITHELIAL-CELLS; INDUCER CELLS; IL-22; SIGNALS; DIFFERENTIATION; RECONSTITUTION; INFLAMMATION; HOMEOSTASIS;

D O I：

10.1126/science.1218004

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Endogenous thymic regeneration is a crucial function that allows for renewal of immune competence after stress, infection, or immunodepletion. However, the mechanisms governing this regeneration remain poorly understood. We detail such a mechanism, centered on interleukin-22 (IL-22) and triggered by the depletion of CD4(+)CD8(+) double-positive thymocytes. Intrathymic levels of IL-22 were increased after thymic insult, and thymic recovery was impaired in IL-22-deficient mice. IL-22, which signaled through thymic epithelial cells and promoted their proliferation and survival, was up-regulated by radio-resistant ROR gamma(t)(+)CCR6(+)NKp46(-) lymphoid tissue inducer cells after thymic injury in an IL-23-dependent manner. Administration of IL-22 enhanced thymic recovery after total body irradiation. These studies reveal mechanisms of endogenous thymic repair and offer innovative regenerative strategies for improving immune competence.

引用

页码：91 / 95

页数：5

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