Interleukin-22 Drives Endogenous Thymic Regeneration in Mice

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Science  01 Mar 2012:
DOI: 10.1126/science.1218004


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 centered on interleukin-22 (IL-22) and triggered by depletion of CD4+CD8+ double positive thymocytes. Intrathymic levels of IL-22 were increased following 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 RORγ(t)+CCR6+NKp46- lymphoid tissue-inducer cells after thymic injury in an IL-23–dependent manner. Importantly, administration of IL-22–enhanced thymic recovery following total body irradiation. These studies reveal mechanisms of endogenous thymic repair and offer innovative regenerative strategies for improving immune competence.