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A tissue checkpoint regulates type 2 immunity.

ABSTRACT: Group 2 innate lymphoid cells (ILC2s) and CD4+ type 2 helper T cells (TH2 cells) are defined by their similar effector cytokines, which together mediate the features of allergic immunity. We found that tissue ILC2s and TH2 cells differentiated independently but shared overlapping effector function programs that were mediated by exposure to the tissue-derived cytokines interleukin 25 (IL-25), IL-33 and thymic stromal lymphopoietin (TSLP). Loss of these three tissue signals did not affect lymph node priming, but abrogated the terminal differentiation of effector TH2 cells and adaptive lung inflammation in a T cell-intrinsic manner. Our findings suggest a mechanism by which diverse perturbations can activate type 2 immunity and reveal a shared local-tissue-elicited checkpoint that can be exploited to control both innate and adaptive allergic inflammation.

SUBMITTER: Van Dyken SJ

PROVIDER: S-EPMC5275767 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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A tissue checkpoint regulates type 2 immunity.

Van Dyken Steven J SJ Nussbaum Jesse C JC Lee Jinwoo J Molofsky Ari B AB Liang Hong-Erh HE Pollack Joshua L JL Gate Rachel E RE Haliburton Genevieve E GE Ye Chun J CJ Marson Alexander A Erle David J DJ Locksley Richard M RM

Nature immunology 20161017 12

Group 2 innate lymphoid cells (ILC2s) and CD4+ type 2 helper T cells (TH2 cells) are defined by their similar effector cytokines, which together mediate the features of allergic immunity. We found that tissue ILC2s and TH2 cells differentiated independently but shared overlapping effector function programs that were mediated by exposure to the tissue-derived cytokines interleukin 25 (IL-25), IL-33 and thymic stromal lymphopoietin (TSLP). Loss of these three tissu ...[more]

PMID: 27749840

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A tissue checkpoint regulates type 2 immunity

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