FcγRIIb inhibits allergic lung inflammation in a murine model of allergic asthma

Nilesh Dharajiya, Swapnil V. Vaidya, Hiroki Murai, Victor Cardenas, Alexander Kurosky, Istvan Boldogh, Sanjiv Sur

Research output: Contribution to journalArticle

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Abstract

Allergic asthma is characterized by airway eosinophilia, increased mucin production and allergen-specific IgE. Fc gamma receptor IIb (FcγRIIb), an inhibitory IgG receptor, has recently emerged as a negative regulator of allergic diseases like anaphylaxis and allergic rhinitis. However, no studies to date have evaluated its role in allergic asthma. Our main objective was to study the role of FcγRIIb in allergic lung inflammation. We used a murine model of allergic airway inflammation. Inflammation was quantified by BAL inflammatory cells and airway mucin production. FcγRIIb expression was measured by qPCR and flow cytometry and the cytokines were quantified by ELISA. Compared to wild type animals, FcγRIIb deficient mice mount a vigorous allergic lung inflammation characterized by increased bronchoalveolar lavage fluid cellularity, eosinophilia and mucin content upon ragweed extract (RWE) challenge. RWE challenge in sensitized mice upregulated FcγRIIb in the lungs. Disruption of IFN-γ gene abrogated this upregulation. Treatment of naïve mice with the Th1-inducing agent CpG DNA increased FcγRIIb expression in the lungs. Furthermore, treatment of sensitized mice with CpG DNA prior to RWE challenge induced greater upregulation of FcγRIIb than RWE challenge alone. These observations indicated that RWE challenge upregulated FcγRIIb in the lungs by IFN-c- and Th1-dependent mechanisms. RWE challenge upregulated FcγRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells. FcγRIIb deficient mice also exhibited an exaggerated RWE-specific IgE response upon sensitization when compared to wild type mice. We propose that FcγRIIb physiologically regulates allergic airway inflammation by two mechanisms: 1) allergen challenge mediates upregulation of FcγRIIb on pulmonary CD14+/MHC II+ mononuclear cells and CD11c+ cells by an IFN-γ dependent mechanism; and 2) by attenuating the allergen specific IgE response during sensitization. Thus, stimulating FcγRIIb may be a therapeutic strategy in allergic airway disorders.

Original languageEnglish (US)
Article numbere9337
JournalPLoS One
Volume5
Issue number2
DOIs
StatePublished - Feb 22 2010

Fingerprint

IgG Receptors
asthma
Pneumonia
Asthma
inflammation
animal models
lungs
Ambrosia
receptors
extracts
mucins
mice
Mucins
Lung
allergens
Allergens
Immunoglobulin E
eosinophilia
Up-Regulation
Eosinophilia

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Dharajiya, N., Vaidya, S. V., Murai, H., Cardenas, V., Kurosky, A., Boldogh, I., & Sur, S. (2010). FcγRIIb inhibits allergic lung inflammation in a murine model of allergic asthma. PLoS One, 5(2), [e9337]. https://doi.org/10.1371/journal.pone.0009337

FcγRIIb inhibits allergic lung inflammation in a murine model of allergic asthma. / Dharajiya, Nilesh; Vaidya, Swapnil V.; Murai, Hiroki; Cardenas, Victor; Kurosky, Alexander; Boldogh, Istvan; Sur, Sanjiv.

In: PLoS One, Vol. 5, No. 2, e9337, 22.02.2010.

Research output: Contribution to journalArticle

Dharajiya, N, Vaidya, SV, Murai, H, Cardenas, V, Kurosky, A, Boldogh, I & Sur, S 2010, 'FcγRIIb inhibits allergic lung inflammation in a murine model of allergic asthma', PLoS One, vol. 5, no. 2, e9337. https://doi.org/10.1371/journal.pone.0009337
Dharajiya, Nilesh ; Vaidya, Swapnil V. ; Murai, Hiroki ; Cardenas, Victor ; Kurosky, Alexander ; Boldogh, Istvan ; Sur, Sanjiv. / FcγRIIb inhibits allergic lung inflammation in a murine model of allergic asthma. In: PLoS One. 2010 ; Vol. 5, No. 2.
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