title: T cells are the critical source of IL-4/IL-13 in a mouse model of allergic asthma.
abstract: 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.
authors.affiliation: Department of Infection Biology, University Hospital Erlangen at the Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Oeser
authors.affiliation: Asthma Core Facility, The Research Center Immunotherapy (FZI) at the University Hospital Mainz, Mainz, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Maxeiner
authors.affiliation: Department of Infection Biology, University Hospital Erlangen at the Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Symowski
authors.affiliation: Asthma Core Facility, The Research Center Immunotherapy (FZI) at the University Hospital Mainz, Mainz, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Stassen
authors.affiliation: Department of Infection Biology, University Hospital Erlangen at the Friedrich-Alexander University Erlangen-Nuremberg (FAU), Erlangen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Voehringer
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism; D020397:Goblet Cells / Q000378:metabolism / Q000473:pathology; D006729:Hormones, Ectopic / Q000378:metabolism; D006965:Hyperplasia; D007113:Immunity, Innate; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D015848:Interleukin-5 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008262:Macrophage Activation / Q000276:immunology; D051379:Mice; D055271:Mucin 5AC / Q000378:metabolism; D009088:Mucoproteins / Q000378:metabolism; D010047:Ovalbumin / Q000009:adverse effects; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D006729:Hormones, Ectopic; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; D018793:Interleukin-13; D015848:Interleukin-5; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009088:Mucoproteins; C486522:Retnlb protein, mouse; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: Asthma; ILC2; Th2 cells; basophils; eosinophils