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Science 336 (6077): 91-95

Copyright © 2012 by the American Association for the Advancement of Science

Interleukin-22 Drives Endogenous Thymic Regeneration in Mice

Jarrod A. Dudakov,1,2,* Alan M. Hanash,3 Robert R. Jenq,3,4 Lauren F. Young,1 Arnab Ghosh,1 Natalie V. Singer,1 Mallory L. West,1 Odette M. Smith,1 Amanda M. Holland,1,5 Jennifer J. Tsai,1,5 Richard L. Boyd,2 Marcel R. M. van den Brink1,3,4,5,*

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 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.

1 Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
2 Monash Immunology and Stem Cell Laboratories, Monash University, Melbourne, Victoria 3800, Australia.
3 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
4 Department of Medicine, Weill Cornell Medical College, New York, NY 10021, USA.
5 Department of Immunology and Microbial Pathogenesis, Weill Cornell Medical College, New York, NY 10021, USA.

* To whom correspondence should be addressed. E-mail: dudakovj{at}mskcc.org (J.A.D.); vandenbm{at}mskcc.org (M.R.M.v.d.B.)

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