title: 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.
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Van Dyken
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Jesse C
authors.initials: JC
authors.lastname: Nussbaum
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Jinwoo
authors.identifier: http://orcid.org/0000-0003-2991-4183
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Ari B
authors.initials: AB
authors.lastname: Molofsky
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Hong-Erh
authors.initials: HE
authors.lastname: Liang
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, USA.|Lung Biology Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Pollack
authors.affiliation: Department of Epidemiology and Biostatistics, Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Gate
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, USA.|Diabetes Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Genevieve E
authors.initials: GE
authors.lastname: Haliburton
authors.affiliation: Department of Epidemiology and Biostatistics, Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Chun J
authors.initials: CJ
authors.lastname: Ye
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, USA.|Diabetes Center, University of California, San Francisco, San Francisco, California, USA.|Innovative Genomics Initiative (IGI), University of California, Berkeley, Berkeley, California, USA.|UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Marson
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, USA.|Lung Biology Center, University of California, San Francisco, San Francisco, California, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Erle
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California, USA.|UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.|Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Locksley
mesh_terms: D056704:Adaptive Immunity; D000485:Allergens / Q000276:immunology; D000818:Animals; D001234:Aspergillus niger; D001514:Bee Venoms / Q000276:immunology; D001516:Bees; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D040001:Dermatophagoides farinae; D006967:Hypersensitivity / Q000276:immunology*; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D000067596:Interleukin-33 / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D000485:Allergens; D001514:Bee Venoms; D016207:Cytokines; C486701:IL25 protein, human; D020381:Interleukin-17; D000067596:Interleukin-33; D000094632:Thymic Stromal Lymphopoietin