Lung Natural Helper Cells Are a Critical Source of Th2 Cell-Type Cytokines in Protease Allergen-Induced Airway Inflammation

• Published in: Immunity (Cambridge, Mass.) Vol. 36; no. 3; pp. 451 - 463
• Main Authors: Halim, Timotheus Y.F., Krauß, Ramona H., Sun, Ann C., Takei, Fumio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.03.2012; Elsevier Limited
• Subjects: Adoptive Transfer; Airway management; Allergens; Allergens - immunology; Animals; Asthma; Asthma - etiology; Asthma - immunology; Asthma - pathology; Cytokines; Cytokines - administration & dosage; Cytokines - biosynthesis; Disease Models, Animal; Experiments; Explants; Flow cytometry; Gene expression; Gene Expression Profiling; Genomes; Helper cells; Immunity, Innate; Interleukin 13; Interleukin 2; Interleukin 5; Interleukin 7; Intranasal administration; Leukocytes (eosinophilic); Lung; Lung - immunology; Lung - pathology; Lungs; Lymphocytes; Lymphocytes T; Medical research; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Mucus; Mucus - secretion; Papain; Papain - immunology; Production capacity; Proteinase; Pulmonary Eosinophilia - etiology; Pulmonary Eosinophilia - immunology; Pulmonary Eosinophilia - pathology; Respiratory tract diseases; Rodents; Stroma; T-Lymphocytes, Helper-Inducer - classification; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - pathology; Th2 Cells - immunology; Th2 Cells - pathology; Thymic stromal lymphopoietin; Thymus
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2011.12.020

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+/loCD25+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. [Display omitted] ► Lung natural helper cells produce large amounts of Th2 cell-type cytokines ► Protease allergen stimulates lung natural helper cells ► Stroma-derived cytokines stimulate lung natural helper cells ► Th2 cell-type cytokines from lung natural helper cells induce T cell-independent asthma