title: Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation.
abstract: Overproduction of cytokines by T helper 2 (Th2) cells in the lung is thought to be a cause of asthma. Here we report that innate lymphocytes termed lung natural helper (LNH) cells are a T cell-independent source of Th2 cell-type cytokines in protease allergen-treated lungs. LNH (Lin(-)Sca-1(+)c-kit(+/lo)CD25(+)CD127(+)) cells, when stimulated by IL-33 plus IL-2, IL-7, or thymic stroma lymphopoietin (TSLP), produced large amounts of IL-5 and IL-13. Intranasal administration of protease allergen papain induced eosinophil infiltration and mucus hyperproduction in the lung of wild-type and Rag1(-/-) mice, but not in Rag2(-/-)Il2rg(-/-) mice that lack LNH cells. LNH cell depletion inhibited papain-induced airway inflammation in Rag1(-/-) mice whereas adoptive transfer of LNH cells enabled Rag2(-/-)Il2rg(-/-) mice to respond to papain. Treatment of lung explants with papain induced IL-33 and TSLP production by stroma cells and IL-5 and IL-13 production by LNH cells. Thus, LNH cells are critical for protease allergen-induced airway inflammation.
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Timotheus Y F
authors.initials: TY
authors.lastname: Halim
authors.forename: Ramona H
authors.initials: RH
authors.lastname: Krauss
authors.forename: Ann C
authors.initials: AC
authors.lastname: Sun
authors.forename: Fumio
authors.initials: F
authors.lastname: Takei
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000008:administration & dosage / Q000096:biosynthesis*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009093:Mucus / Q000378:metabolism; D010206:Papain / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000276:immunology / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
chemical_list: D000485:Allergens; D016207:Cytokines; D010206:Papain