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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Cell Count
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Cell Proliferation
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Cell Survival
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Dendritic Cells / physiology
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Epithelial Cells / cytology
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Epithelial Cells / physiology
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Interleukin-22
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Interleukin-23 / metabolism
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Interleukins / administration & dosage
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Interleukins / deficiency
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Interleukins / genetics
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Interleukins / metabolism*
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Lymphocytes / cytology
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Lymphocytes / physiology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
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Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
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Radiation Dosage
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Receptors, Interleukin / metabolism
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Recombinant Proteins / administration & dosage
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Regeneration*
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Signal Transduction
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Thymocytes / physiology*
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Thymus Gland / cytology
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Thymus Gland / immunology
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Thymus Gland / physiology*
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Thymus Gland / radiation effects
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Up-Regulation
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Whole-Body Irradiation
Substances
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Interleukin-23
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Interleukins
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Interleukin
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Recombinant Proteins
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Rorc protein, mouse
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interleukin-22 receptor