Interleukin-22 drives endogenous thymic regeneration in mice |
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Authors: | Dudakov Jarrod A Hanash Alan M Jenq Robert R Young Lauren F Ghosh Arnab Singer Natalie V West Mallory L Smith Odette M Holland Amanda M Tsai Jennifer J Boyd Richard L van den Brink Marcel R M |
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Institution: | Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. dudakovj@mskcc.org |
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Abstract: | 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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