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Potential contribution of IL-7 to allergen-induced eosinophilic airway inflammation in asthma.
J Immunol. 2009 Feb 01; 182(3):1404-10.JI

Abstract

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 alpha (CD127) and its common gamma 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.

Authors+Show Affiliations

Section of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA. eak@medicine.wisc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

19155487

Citation

Kelly, Elizabeth A B., et al. "Potential Contribution of IL-7 to Allergen-induced Eosinophilic Airway Inflammation in Asthma." Journal of Immunology (Baltimore, Md. : 1950), vol. 182, no. 3, 2009, pp. 1404-10.
Kelly EA, Koziol-White CJ, Clay KJ, et al. Potential contribution of IL-7 to allergen-induced eosinophilic airway inflammation in asthma. J Immunol. 2009;182(3):1404-10.
Kelly, E. A., Koziol-White, C. J., Clay, K. J., Liu, L. Y., Bates, M. E., Bertics, P. J., & Jarjour, N. N. (2009). Potential contribution of IL-7 to allergen-induced eosinophilic airway inflammation in asthma. Journal of Immunology (Baltimore, Md. : 1950), 182(3), 1404-10.
Kelly EA, et al. Potential Contribution of IL-7 to Allergen-induced Eosinophilic Airway Inflammation in Asthma. J Immunol. 2009 Feb 1;182(3):1404-10. PubMed PMID: 19155487.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potential contribution of IL-7 to allergen-induced eosinophilic airway inflammation in asthma. AU - Kelly,Elizabeth A B, AU - Koziol-White,Cynthia J, AU - Clay,Kathryn J, AU - Liu,Lin Ying, AU - Bates,Mary Ellen, AU - Bertics,Paul J, AU - Jarjour,Nizar N, PY - 2009/1/22/entrez PY - 2009/1/22/pubmed PY - 2009/3/31/medline SP - 1404 EP - 10 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 182 IS - 3 N2 - 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 alpha (CD127) and its common gamma 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. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/19155487/Potential_contribution_of_IL_7_to_allergen_induced_eosinophilic_airway_inflammation_in_asthma_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&amp;pmid=19155487 DB - PRIME DP - Unbound Medicine ER -