Lung natural helper cells are a critical source of Th2 cell-type cytokines in protease allergen-induced airway inflammation

Immunity. 2012 Mar 23;36(3):451-63. doi: 10.1016/j.immuni.2011.12.020. Epub 2012 Mar 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Allergens / immunology
  • Animals
  • Asthma / etiology
  • Asthma / immunology*
  • Asthma / pathology
  • Cytokines / administration & dosage
  • Cytokines / biosynthesis*
  • Disease Models, Animal
  • Gene Expression Profiling
  • Immunity, Innate
  • Lung / immunology*
  • Lung / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Mucus / metabolism
  • Papain / immunology
  • Pulmonary Eosinophilia / etiology
  • Pulmonary Eosinophilia / immunology
  • Pulmonary Eosinophilia / pathology
  • T-Lymphocytes, Helper-Inducer / classification
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / pathology
  • Th2 Cells / immunology
  • Th2 Cells / pathology


  • Allergens
  • Cytokines
  • Papain

Associated data

  • GEO/GSE6057