A tissue checkpoint regulates type 2 immunity

SJ Van Dyken, JC Nussbaum, J Lee, AB Molofsky… - Nature …, 2016 - nature.com
SJ Van Dyken, JC Nussbaum, J Lee, AB Molofsky, HE Liang, JL Pollack, RE Gate…
Nature immunology, 2016nature.com
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 …
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.
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