Interleukin-22 drives endogenous thymic regeneration in mice

JA Dudakov, AM Hanash, RR Jenq, LF Young… - Science, 2012 - science.org
JA Dudakov, AM Hanash, RR Jenq, LF Young, A Ghosh, NV Singer, ML West, OM Smith…
Science, 2012science.org
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 …
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 RORγ(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.
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