T cells are the critical source of IL-4/IL-13 in a mouse model of allergic asthma

Allergy. 2015 Nov;70(11):1440-9. doi: 10.1111/all.12705. Epub 2015 Aug 20.


Background: IL-4 and IL-13 play a crucial role during allergic asthma. Both cytokines can be produced by T cells and a variety of cell types of the innate immune system. The relative contribution of T-cell-derived vs innate IL-4/IL-13 for allergic inflammation and airway hyperreactivity remains unclear.

Methods: We compared the severity of OVA/alum-induced allergic lung inflammation in WT BALB/c mice to mice that lack expression of IL-4/IL-13 only in T cells (4-13Tko) or in all cell types (4-13ko).

Results: T-cell-derived IL-4/IL-13 was required for IgG1 and IgE production, recruitment of eosinophils and basophils to the lung, goblet cell hyperplasia, expression of Muc5ac, Clca3, and RELMβ, differentiation of alternatively activated macrophages, and airway hyperreactivity. Interestingly, ILC2 recruitment to the lung occurred independently of T-cell-derived IL-4/IL-13 but was diminished in the absence of IL-4/IL-13 from all cell types. Thus, the number of IL-4/IL-13-competent ILC2s did not correlate with the severity of lung pathology.

Conclusions: Th2 cells appear to be the critical IL-4/IL-13-expressing cell type for the induction of allergic airway inflammation and airway hyperreactivity. The translational perspective of our results indicates that inhibition or reprogramming of Th2 cells may be very effective for the treatment of allergic asthma.

Keywords: Asthma; ILC2; Th2 cells; basophils; eosinophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / immunology*
  • Asthma / metabolism*
  • Asthma / pathology
  • Basophils / immunology
  • Basophils / metabolism
  • Chloride Channels / metabolism
  • Disease Models, Animal
  • Eosinophils / immunology
  • Eosinophils / metabolism
  • Goblet Cells / metabolism
  • Goblet Cells / pathology
  • Hormones, Ectopic / metabolism
  • Hyperplasia
  • Immunity, Innate
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-13 / metabolism*
  • Interleukin-4 / metabolism*
  • Interleukin-5 / biosynthesis
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Macrophage Activation / immunology
  • Mice
  • Mucin 5AC / metabolism
  • Mucoproteins / metabolism
  • Ovalbumin / adverse effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Th2 Cells / immunology
  • Th2 Cells / metabolism


  • Chloride Channels
  • Clca3a1 protein, mouse
  • Hormones, Ectopic
  • Immunoglobulin G
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-13
  • Interleukin-5
  • Muc5ac protein, mouse
  • Mucin 5AC
  • Mucoproteins
  • Retnlb protein, mouse
  • Interleukin-4
  • Immunoglobulin E
  • Ovalbumin