Interleukin-22 Drives Endogenous Thymic Regeneration in Mice

被引：291
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
收藏
页码：91 / 95
页数：5
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