Critical role of the Fc receptor γ-chain on APCs in the development of allergen-induced airway hyperresponsiveness and inflammation

Kenichi Kitamura, Katsuyuki Takeda, Toshiyuki Koya, Nobuaki Miyahara, Taku Kodama, Azzeddine Dakhama, Toshiyuki Takai, Atsushi Hirano, Mitsune Tanimoto, Mine Harada, Erwin W. Gelfand

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28 Citations (Scopus)

Abstract

The FcR common γ-chain (FcRγ) is an essential component of the receptors FcεRI, FcγRI, and FcγRIII, which are expressed on many inflammatory cell types. The role of these receptors in the initiation or maintenance of allergic inflammation has not been well defined. FcRγ-deficient (FcRγ-/-) and control (wild-type (WT)) mice were sensitized and subsequently challenged with OVA. Following sensitization and challenge to OVA, FcRγ-deflcient (FcRγ -/-) mice developed comparable levels of IgE and IgG1 as WT mice. However, numbers of eosinophils, levels of IL-5, IL-13, and eotaxin in bronchoalveolar lavage fluid, and mononuclear cell (MNC) proliferative responses to OVA were significantly reduced, as was airway hyperresponsiveness (AHR) to inhaled methacholine. Reconstitution of FcRγ-/- mice with whole spleen MNC from WT mice before sensitization restored development of AHR and the numbers of eosinophils in bronchoalveolar lavage fluid; reconstitution after sensitization but before OVA challenge only partially restored these responses. These responses were also restored when FcRγ-/- mice received T cell-depleted MNC, T and B cell-depleted MNC, or bone marrow-derived dendritic cells before sensitization from FcR+/+ or FcγRIII-deficient but not FcRγ-/- mice. The expression levels of FcγRIV on bone marrow-derived dendritic cells from FcR+/+ mice were found to be low. These results demonstrate that expression of FcRγ, most likely FcγRI, on APCs is important during the sensitization phase for the development of allergic airway inflammation and AHR.

Original languageEnglish
Pages (from-to)480-488
Number of pages9
JournalJournal of Immunology
Volume178
Issue number1
DOIs
Publication statusPublished - Jan 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kitamura, K., Takeda, K., Koya, T., Miyahara, N., Kodama, T., Dakhama, A., Takai, T., Hirano, A., Tanimoto, M., Harada, M., & Gelfand, E. W. (2007). Critical role of the Fc receptor γ-chain on APCs in the development of allergen-induced airway hyperresponsiveness and inflammation. Journal of Immunology, 178(1), 480-488. https://doi.org/10.4049/jimmunol.178.1.480