Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 124, Issue 3, Pages 573-U269Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2009.04.031
Keywords
Adoptive transfer; airway hyperresponsiveness; asthma; eosinophil; IFN-gamma; lung inflammation; severe combined immunodeficiency
Categories
Funding
- European Union (Feder and Interreg)
- Nord-Pas-de-Calais Region (ARCIR)
- Fondation pour la Recherche Medicale (FRM)
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Background: Eosinophils are key players in T(H)2-driven pathologies, such as allergic lung inflammation. After IL-5- and eotaxin-mediated tissue recruitment, they release several cytotoxic and inflammatory mediators. However, their exact contribution to asthma remains controversial. Indeed, in human subjects anti-IL-5 treatment inhibits eosinophilia but not antigen-induced airway hyperresponsiveness (AHR). Likewise, lung fibrosis is abrogated in 2 strains of eosinophil-deficient mice, whereas AHR is inhibited in only one of them. Finally, eosinophils have been shown to attract T(H)2 lymphocytes at the inflammatory site. Objective: The ability of eosinophils to promote AHR and lung inflammation independently of lymphocytes was investigated. Methods: Adoptive transfers of resting or activated eosinophils from IL-5 transgenic mice were performed into naive BALB/c mice, mice with severe combined immunodeficiency, and IFN-gamma-deficient BALB/c recipients. Results: Adoptively transferred eosinophils induced lung inflammation, fibrosis, collagen deposition, and AHR not only in BALB/c mice but also in recipient mice with severe combined immunodeficiency. Surprisingly, IFN-gamma expression was increased in lungs from eosinophil-transferred animals. Furthermore, IFN-gamma neutralization in recipients partially inhibited eosinophil- induced AHR. Moreover, IFN-gamma-deficient eosinophils or eosinophils treated with a blocking anti-IFN-gamma receptor antibody failed to induce AHR in IFN-gamma-deficient recipients. Finally, in vitro and at low concentrations, IFN-gamma increased eosinophil peroxidase release, potentiated chemotaxis, and prolonged survival, suggesting the existence of an autocrine mechanism. Conclusions: These results support the important and previously unsuspected contribution of eosinophils to lung inflammation independently of lymphocytes through production of IFN-gamma, the prototypical T(H)1 cytokine. (J Allergy Clin Immunol 2009;124:573-82.)
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