Immunity
Volume 36, Issue 3, 23 March 2012, Pages 451-463
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Article
Lung Natural Helper Cells Are a Critical Source of Th2 Cell-Type Cytokines in Protease Allergen-Induced Airway Inflammation

https://doi.org/10.1016/j.immuni.2011.12.020Get rights and content
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Summary

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 (LinSca-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.

Highlights

► 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

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