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* Section of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and
Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792
The primary function of IL-7 is to promote maturation and survival of T cells. Through microarray expression analysis, we previously observed that human blood eosinophils express mRNA for IL-7R
(CD127) and its common 
chain (CD132). The purpose of this study was to determine whether eosinophils have functional IL-7 receptors and to assess the potential contribution of IL-7 to eosinophilic airway inflammation by evaluating its presence in bronchoalveolar lavage (BAL) fluid of subjects with atopic asthma before and after segmental bronchoprovocation with allergen. Immunoblot analysis revealed that CD127 is present in highly purified human blood eosinophils. Furthermore, eosinophils responded to IL-7 with phosphorylation of STAT5, up-regulation of the activation marker CD69, and prolonged survival. Neutralization of GM-CSF but not IL-5 significantly blunted these functional responses, suggesting that IL-7 mediates its effects by promoting eosinophil release of autologous GM-CSF. Notably, the suppressive effect of anti-GM-CSF on STAT5 phosphorylation occurred within 10 min of eosinophil exposure to IL-7. Thus, IL-7 likely activates eosinophil release of preformed rather than newly synthesized GM-CSF. The biological relevance of IL-7 to eosinophilia in vivo was implicated in a study of airway allergen challenge in patients with allergic asthma. IL-7 concentrations in BAL fluid increased significantly 48 h after segmental allergen challenge and were highly correlated with BAL eosinophils (r = 0.7, p < 0.001). In conclusion, the airway response to allergen is associated with the generation of IL-7, which may contribute to airway inflammation by promoting enhanced eosinophil activation and survival. Activation of eosinophils is a novel function for IL-7.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by an institutional Specialized Center of Research Grant HL56396 from the National Institutes of Health, a Program Project Grant HL088584 from the National Institutes of Health, and the University of Wisconsin General Clinical Research Center Grant M01RR03186 from the National Institutes of Health.
2 Address correspondence and reprint requests to Dr. Elizabeth A. (Becky) Kelly, Section of Allergy, Pulmonary and Critical Care Medicine, CSC K4/928, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792-9988, E-mail address: eak{at}medicine.wisc.edu
3 Abbreviations used in this paper: c, common chain; BAL, bronchoalveolar lavage; SBP, segmental bronchoprovocation.
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  J. Carlens, B. Wahl, M. Ballmaier, S. Bulfone-Paus, R. Forster, and O. Pabst Common {gamma}-Chain-Dependent Signals Confer Selective Survival of Eosinophils in the Murine Small Intestine J. Immunol., November 1, 2009; 183(9): 5600 - 5607. [Abstract] [Full Text] [PDF]
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