Computational and experimental analysis reveals a requirement for eosinophil-derived IL-13 for the development of allergic airway responses in C57BL/6 mice

J Immunol. 2011 Mar 1;186(5):2936-49. doi: 10.4049/jimmunol.1001148. Epub 2011 Feb 2.

Abstract

Eosinophils are found in the lungs of humans with allergic asthma, as well as in the lungs of animals in models of this disease. Increasing evidence suggests that these cells are integral to the development of allergic asthma in C57BL/6 mice. However, the specific function of eosinophils that is required for this event is not known. In this study, we experimentally validate a dynamic computational model and perform follow-up experimental observations to determine the mechanism of eosinophil modulation of T cell recruitment to the lung during development of allergic asthma. We find that eosinophils deficient in IL-13 were unable to rescue airway hyperresponsiveness, T cell recruitment to the lungs, and Th2 cytokine/chemokine production in ΔdblGATA eosinophil-deficient mice, even if Th2 cells were present. However, eosinophil-derived IL-13 alone was unable to rescue allergic asthma responses in the absence of competence of other IL-13-producing cells. We further computationally investigate the role of other cell types in the production of IL-13, which led to the various predictions including early and late pulses of IL-13 during airway hyperresponsiveness. These experiments suggest that eosinophils and T cells have an interdependent relationship, centered on IL-13, which regulates T cell recruitment to the lung and development of allergic asthma.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Validation Study

MeSH terms

  • Airway Resistance / genetics
  • Airway Resistance / immunology
  • Animals
  • Bronchial Hyperreactivity / genetics
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / pathology
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Computer Simulation
  • Disease Models, Animal*
  • Eosinophils / immunology*
  • Eosinophils / metabolism
  • Eosinophils / pathology
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-13 / deficiency
  • Interleukin-13 / metabolism
  • Interleukin-13 / physiology*
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Immunological*
  • Ovalbumin / immunology
  • Ovalbumin / toxicity
  • Random Allocation
  • Respiratory Hypersensitivity / genetics
  • Respiratory Hypersensitivity / immunology*
  • Respiratory Hypersensitivity / pathology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Th2 Cells / pathology

Substances

  • Interleukin-13
  • Ovalbumin