Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation

Immunity. 2014 Mar 20;40(3):425-35. doi: 10.1016/j.immuni.2014.01.011. Epub 2014 Mar 6.


Naive CD4(+) T cell differentiation into distinct subsets of T helper (Th) cells is a pivotal process in the initiation of the adaptive immune response. Allergens predominantly stimulate Th2 cells, causing allergic inflammation. However, why allergens induce Th2 cell differentiation is not well understood. Here we show that group 2 innate lymphoid cells (ILC2s) are required to mount a robust Th2 cell response to the protease-allergen papain. Intranasal administration of papain stimulated ILC2s and Th2 cells, causing allergic lung inflammation and elevated immunoglobulin E titers. This process was severely impaired in ILC2-deficient mice. Whereas interleukin-4 (IL-4) was dispensable for papain-induced Th2 cell differentiation, ILC2-derived IL-13 was critical as it promoted migration of activated lung dendritic cells into the draining lymph node where they primed naive T cells to differentiate into Th2 cells. Papain-induced ILC2 activation and Th2 cell differentiation was IL-33-dependent, suggesting a common pathway in the initiation of Th2 cell responses to allergen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Allergens / administration & dosage
  • Allergens / immunology
  • Animals
  • CD40 Antigens / metabolism
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Movement / immunology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology*
  • Immunity, Innate*
  • Interleukin-13 / metabolism
  • Interleukin-13 / pharmacology
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Lymph Nodes / immunology
  • Mice
  • Mice, Knockout
  • Papain / immunology
  • Pneumonia / genetics
  • Pneumonia / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Th2 Cells / cytology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology


  • Allergens
  • CD40 Antigens
  • Interleukin-13
  • Interleukin-4
  • Papain