Interleukin-22 drives endogenous thymic regeneration in mice

Jarrod A Dudakov; Alan M Hanash; Robert R Jenq; Lauren F Young; Arnab Ghosh; Natalie V Singer; Mallory L West; Odette M Smith; Amanda M Holland; Jennifer J Tsai; Richard L Boyd; Marcel R M van den Brink

doi:10.1126/science.1218004

Interleukin-22 drives endogenous thymic regeneration in mice

Jarrod A Dudakov, Alan M Hanash, Robert R Jenq, Lauren F Young, Arnab Ghosh, Natalie V Singer, Mallory L West, Odette M Smith, Amanda M Holland, Jennifer J Tsai, Richard L Boyd, Marcel R M van den Brink

Research output: Contribution to journal › Article › Research › peer-review

297 Citations (Scopus)

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 RORgamma(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.

Original language	English
Pages (from-to)	91 - 95
Number of pages	5
Journal	Science
Volume	336
Issue number	6077
DOIs	https://doi.org/10.1126/science.1218004
Publication status	Published - 2012

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title = "Interleukin-22 drives endogenous thymic regeneration in mice",

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 RORgamma(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.",

author = "Dudakov, {Jarrod A} and Hanash, {Alan M} and Jenq, {Robert R} and Young, {Lauren F} and Arnab Ghosh and Singer, {Natalie V} and West, {Mallory L} and Smith, {Odette M} and Holland, {Amanda M} and Tsai, {Jennifer J} and Boyd, {Richard L} and {van den Brink}, {Marcel R M}",

year = "2012",

doi = "10.1126/science.1218004",

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volume = "336",

pages = "91 -- 95",

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T1 - Interleukin-22 drives endogenous thymic regeneration in mice

AU - Dudakov, Jarrod A

AU - Hanash, Alan M

AU - Jenq, Robert R

AU - Young, Lauren F

AU - Ghosh, Arnab

AU - Singer, Natalie V

AU - West, Mallory L

AU - Smith, Odette M

AU - Holland, Amanda M

AU - Tsai, Jennifer J

AU - Boyd, Richard L

AU - van den Brink, Marcel R M

PY - 2012

Y1 - 2012

N2 - 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 RORgamma(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.

AB - 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 RORgamma(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.

UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22383805

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DO - 10.1126/science.1218004

M3 - Article

SN - 0036-8075

VL - 336

SP - 91

EP - 95

JO - Science

JF - Science

IS - 6077

ER -

Interleukin-22 drives endogenous thymic regeneration in mice

Abstract

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