A tissue checkpoint regulates type 2 immunity

Steven J. Van Dyken; Jesse C. Nussbaum; Jinwoo Lee; Ari B. Molofsky; Hong Erh Liang; Joshua L. Pollack; Rachel E. Gate; Genevieve E. Haliburton; Chun J. Ye; Alexander Marson; David J. Erle; Richard M. Locksley

doi:10.1038/ni.3582

A tissue checkpoint regulates type 2 immunity

Steven J. Van Dyken, Jesse C. Nussbaum, Jinwoo Lee, Ari B. Molofsky, Hong Erh Liang, Joshua L. Pollack, Rachel E. Gate, Genevieve E. Haliburton, Chun J. Ye, Alexander Marson, David J. Erle, Richard M. Locksley

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

197 Scopus citations

Abstract

Group 2 innate lymphoid cells (ILC2s) and CD4 + type 2 helper T cells (T H 2 cells) are defined by their similar effector cytokines, which together mediate the features of allergic immunity. We found that tissue ILC2s and T H 2 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 T H 2 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.

Original language	English
Pages (from-to)	1381-1387
Number of pages	7
Journal	Nature immunology
Volume	17
Issue number	12
DOIs	https://doi.org/10.1038/ni.3582
State	Published - Dec 1 2016

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title = "A tissue checkpoint regulates type 2 immunity",

abstract = "Group 2 innate lymphoid cells (ILC2s) and CD4 + type 2 helper T cells (T H 2 cells) are defined by their similar effector cytokines, which together mediate the features of allergic immunity. We found that tissue ILC2s and T H 2 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 T H 2 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.",

author = "{Van Dyken}, {Steven J.} and Nussbaum, {Jesse C.} and Jinwoo Lee and Molofsky, {Ari B.} and Liang, {Hong Erh} and Pollack, {Joshua L.} and Gate, {Rachel E.} and Haliburton, {Genevieve E.} and Ye, {Chun J.} and Alexander Marson and Erle, {David J.} and Locksley, {Richard M.}",

note = "Funding Information: We thank M. Ji, K. Davis, M. Consengco and Z. Wang for technical expertise, A. Barczak and R. Barbeau for assistance with RNA-Seq, A. McKenzie, S. Akira, S. Ziegler and the US National Institutes of Health Tetramer Core Facility for reagents, and A. Abbas and M. Ansel for comments on the manuscript. Supported by the US National Institutes of Health (AI026918, AI030663, HL107202, HL128903, K08AI113143 and DP5-OD12178), the Howard Hughes Medical Institute and the Sandler Asthma Basic Research Center at the University of California San Francisco.",

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AU - Lee, Jinwoo

AU - Molofsky, Ari B.

AU - Liang, Hong Erh

AU - Pollack, Joshua L.

AU - Gate, Rachel E.

AU - Haliburton, Genevieve E.

AU - Ye, Chun J.

AU - Marson, Alexander

AU - Erle, David J.

AU - Locksley, Richard M.

N1 - Funding Information: We thank M. Ji, K. Davis, M. Consengco and Z. Wang for technical expertise, A. Barczak and R. Barbeau for assistance with RNA-Seq, A. McKenzie, S. Akira, S. Ziegler and the US National Institutes of Health Tetramer Core Facility for reagents, and A. Abbas and M. Ansel for comments on the manuscript. Supported by the US National Institutes of Health (AI026918, AI030663, HL107202, HL128903, K08AI113143 and DP5-OD12178), the Howard Hughes Medical Institute and the Sandler Asthma Basic Research Center at the University of California San Francisco.

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A tissue checkpoint regulates type 2 immunity

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