Interleukin-22 drives endogenous thymic regeneration in mice.
Interleukin-22 drives endogenous thymic regeneration in mice.
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DOI:
10.1126/science.1218004
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发表时间:
2012-04-06
期刊:
影响因子:
--
通讯作者:
van den Brink MR
中科院分区:
文献类型:
--
作者:
Dudakov JA;Hanash AM;Jenq RR;Young LF;Ghosh A;Singer NV;West ML;Smith OM;Holland AM;Tsai JJ;Boyd RL;van den Brink MR
Endogenous thymic regeneration is a crucial function that allows for renewal of immune competence after stress, infection or immunodepletion. The mechanisms governing this regeneration, however, remain poorly understood. Here we detail a framework of thymic regeneration centred on IL-22 and triggered by depletion of CD4+CD8+ double positive (DP) thymocytes. Intrathymic levels of IL-22 were increased following thymic insult, and thymic recovery was impaired in IL-22-deficient mice. IL-22, which signalled through thymic epithelial cells (TECs) and promoted their proliferation and survival, was upregulated by radio-resistant RORγ(t)+CCR6+NKp46− lymphoid tissue-inducer cells (LTi) after thymic injury in an IL-23 dependent manner. Importantly, administration of IL-22 enhanced thymic recovery following total body irradiation (TBI). These studies reveal mechanisms of endogenous thymic repair and offer innovative regenerative strategies for improving immune competence.
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期刊:
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