{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:59:27Z","timestamp":1791255567028,"version":"4.1.0"},"reference-count":55,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2009,2,1]],"date-time":"2009-02-01T00:00:00Z","timestamp":1233446400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u03b1 (CD127) and its common \u03b3 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 &amp;lt; 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.<\/jats:p>","DOI":"10.4049\/jimmunol.182.3.1404","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:01:40Z","timestamp":1397847700000},"page":"1404-1410","source":"Crossref","is-referenced-by-count":55,"title":["Potential Contribution of IL-7 to Allergen-Induced Eosinophilic Airway Inflammation in Asthma"],"prefix":"10.1093","volume":"182","author":[{"given":"Elizabeth A B","family":"Kelly","sequence":"first","affiliation":[{"name":"Section of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia J","family":"Koziol-White","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn J","family":"Clay","sequence":"additional","affiliation":[{"name":"Section of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Section of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Ellen","family":"Bates","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J","family":"Bertics","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin School of Medicine and Public Health , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nizar N","family":"Jarjour","sequence":"additional","affiliation":[{"name":"Section of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,2,1]]},"reference":[{"key":"2026012806224655900_R1","first-page":"110","article-title":"Interleukin-7 receptor \u03b1 (IL-7R\u03b1) deficiency: cellular and molecular bases: analysis of clinical, immunological, and molecular features in 16 novel patients.","volume-title":"Immunol. Rev.","year":"2005"},{"key":"2026012806224655900_R2","first-page":"67","article-title":"Cytokines and immunodeficiency diseases: critical roles of the \u03b3c-dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways.","volume-title":"Immunol. Rev.","year":"2004"},{"key":"2026012806224655900_R3","first-page":"289","article-title":"Cytokine signals in T-cell homeostasis.","volume-title":"J. Immunother.","year":"2005"},{"key":"2026012806224655900_R4","first-page":"1222","article-title":"IL-7 in allogeneic transplant: clinical promise and potential pitfalls.","volume-title":"Leukocyte Lymphoma","year":"2006"},{"key":"2026012806224655900_R5","first-page":"1421","article-title":"IL-7 as a potential therapy for HIV-1-infected individuals.","volume-title":"Expert. Opin. Biol. Ther.","year":"2005"},{"key":"2026012806224655900_R6","first-page":"1701","article-title":"Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets.","volume-title":"J. Exp. Med.","year":"2008"},{"key":"2026012806224655900_R7","first-page":"2670","article-title":"Interleukin-7-mediated inflammation in unstable angina: possible role of chemokines and platelets.","volume-title":"Circulation","year":"2003"},{"key":"2026012806224655900_R8","first-page":"911","article-title":"Interleukin-7 (IL-7) and IL-7 receptor (IL-7R) signalling complex in human solid tumours.","volume-title":"Histol. Histopathol.","year":"2003"},{"key":"2026012806224655900_R9","first-page":"4737","article-title":"IL-7 is essential for the development and the persistence of chronic colitis.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012806224655900_R10","first-page":"275","article-title":"The immunogenetics of multiple sclerosis.","volume-title":"Immunogenetics","year":"2008"},{"key":"2026012806224655900_R11","first-page":"753","article-title":"Interleukin-7 in rheumatoid arthritis.","volume-title":"Rheumatology","year":"2008"},{"key":"2026012806224655900_R12","first-page":"513","article-title":"Cell biology of IL-7, a key lymphotrophin.","volume-title":"Cytokine Growth Factor Rev.","year":"2005"},{"key":"2026012806224655900_R13","first-page":"923","article-title":"Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes.","volume-title":"J. Exp. Med.","year":"1991"},{"key":"2026012806224655900_R14","first-page":"163","article-title":"IL-7 receptor is present on human microvascular endothelial cells.","volume-title":"Immunol. Lett.","year":"2003"},{"key":"2026012806224655900_R15","first-page":"931","article-title":"IL-7 inhibits fibroblast TGF-\u03b2 production and signaling in pulmonary fibrosis.","volume-title":"J. Clin. Invest.","year":"2002"},{"key":"2026012806224655900_R16","first-page":"2992","article-title":"The supportive effects of IL-7 on eosinophil progenitors from human bone marrow cells can be blocked by anti-IL-5.","volume-title":"J. Immunol.","year":"1992"},{"key":"2026012806224655900_R17","first-page":"736","article-title":"Expression of IL-5- and GM-CSF-responsive genes in blood and airway eosinophils.","volume-title":"Am. J. Respir. Cell Mol. Biol.","year":"2004"},{"key":"2026012806224655900_R18","first-page":"18","article-title":"Eosinophils and asthma.","volume-title":"Curr. Allergy Asthma Rep.","year":"2007"},{"key":"2026012806224655900_R19","first-page":"4840","article-title":"Generation of Th1 and Th2 chemokines by human eosinophils: evidence for a critical role of TNF-\u03b1.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012806224655900_R20","first-page":"589","article-title":"Human airway and peripheral blood eosinophils enhance Th1 and Th2 cytokine secretion.","volume-title":"Allergy","year":"2006"},{"key":"2026012806224655900_R21","first-page":"5909","article-title":"Cutting edge: human eosinophils regulate T cell subset selection through indoleamine 2,3-dioxygenase.","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012806224655900_R22","first-page":"1313","article-title":"Eosinophils: singularly destructive effector cells or purveyors of immunoregulation?.","volume-title":"J. Allergy Clin. Immunol.","year":"2007"},{"key":"2026012806224655900_R23","first-page":"556","article-title":"Chemokine receptor expression on human eosinophils from peripheral blood and bronchoalveolar lavage fluid following segmental antigen challenge.","volume-title":"J. Allergy Clin. Immunol.","year":"2003"},{"key":"2026012806224655900_R24","first-page":"6409","article-title":"IL-5 and granulocyte-macrophage colony-stimulating factor activate STAT3 and STAT5 and promote Pim-1 and cyclin D3 protein expression in human eosinophils.","volume-title":"J. Immunol.","year":"2004"},{"key":"2026012806224655900_R25","first-page":"1465","article-title":"Increased airway inflammation with segmental versus aerosol antigen challenge.","volume-title":"Am. Rev. Respir. Dis.","year":"1993"},{"key":"2026012806224655900_R26","first-page":"6452","article-title":"Decreased expression of membrane IL-5R\u03b1 on human eosinophils: I. Loss of membrane IL-5\u03b1 on eosinophils and increased soluble IL-5R\u03b1 in the airway after antigen challenge.","volume-title":"J. Immunol.","year":"2002"},{"key":"2026012806224655900_R27","first-page":"1421","article-title":"The effect of segmental bronchoprovocation with allergen on airway lymphocyte function.","volume-title":"Am. J. Respir. Crit. Care Med.","year":"1997"},{"key":"2026012806224655900_R28","first-page":"27","article-title":"Interleukin-2 induces peroxide production by primed normodense eosinophils of patients with asthma.","volume-title":"Allergy Asthma Proc.","year":"2003"},{"key":"2026012806224655900_R29","first-page":"834","article-title":"Interleukin-2 primes eosinophil degranulation in hypereosinophilia and Wells\u2019 syndrome.","volume-title":"Eur. J. Immunol.","year":"2003"},{"key":"2026012806224655900_R30","first-page":"117","article-title":"Minute quantities of granulocyte-macrophage colony-stimulating factor prolong eosinophil survival.","volume-title":"J. Interferon Cytokine Res.","year":"2001"},{"key":"2026012806224655900_R31","first-page":"6217","article-title":"Engagement of \u03b14\u03b27 integrins by monoclonal antibodies or ligands enhances survival of human eosinophils in vitro.","volume-title":"J. Immunol.","year":"1999"},{"key":"2026012806224655900_R32","first-page":"6780","article-title":"Hyaluronic acid or TNF-\u03b1 plus fibronectin triggers granulocyte macrophage-colony-stimulating factor mRNA stabilization in eosinophils yet engages differential intracellular pathways and mRNA binding proteins.","volume-title":"J. Immunol.","year":"2003"},{"key":"2026012806224655900_R33","first-page":"404","article-title":"Interleukin-15 inhibits spontaneous apoptosis in human eosinophils via autocrine production of granulocyte macrophage-colony stimulating factor and nuclear factor-\u03baB activation.","volume-title":"Am. J. Respir. Cell Mol. Biol.","year":"2002"},{"key":"2026012806224655900_R34","first-page":"281","article-title":"CD69 is expressed by human eosinophils activated in vivo in asthma and in vitro by cytokines.","volume-title":"Immunology","year":"1993"},{"key":"2026012806224655900_R35","first-page":"982","article-title":"Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP.","volume-title":"J. Allergy Clin. Immunol.","year":"2001"},{"key":"2026012806224655900_R36","first-page":"2566","article-title":"The role of Stat5a and Stat5b in signaling by IL-2 family cytokines.","volume-title":"Oncogene","year":"2000"},{"key":"2026012806224655900_R37","first-page":"2035","article-title":"IL-7 up-regulates the expression of IL-8 from resting and stimulated human blood monocytes.","volume-title":"J. Immunol.","year":"1992"},{"key":"2026012806224655900_R38","first-page":"1965","article-title":"CD11c+ eosinophils in the murine thymus: developmental regulation and recruitment upon MHC class I-restricted thymocyte deletion.","volume-title":"J. Immunol.","year":"2000"},{"key":"2026012806224655900_R39","first-page":"655","article-title":"Presence of eosinophilic precursors in the human thymus: evidence for intra-thymic differentiation of cells in eosinophilic lineage.","volume-title":"Pathol. Int.","year":"1995"},{"key":"2026012806224655900_R40","first-page":"2774","article-title":"Mechanisms of rejection induced by tumor cell-targeted gene transfer of interleukin 2, interleukin 4, interleukin 7, tumor necrosis factor, or interferon \u03b3.","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1993"},{"key":"2026012806224655900_R41","first-page":"3931","article-title":"Genetic modification of a murine fibrosarcoma to produce interleukin 7 stimulates host cell infiltration and tumor immunity.","volume-title":"Cancer Res.","year":"1992"},{"key":"2026012806224655900_R42","first-page":"389","article-title":"Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa.","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026012806224655900_R43","first-page":"5673","article-title":"IL-7 deficiency prevents development of a non-T cell non-B cell-mediated colitis.","volume-title":"J. Immunol.","year":"1998"},{"key":"2026012806224655900_R44","first-page":"2579","article-title":"Association of granulocyte-macrophage colony-stimulating factor with the crystalloid granules of human eosinophils.","volume-title":"Am. Soc. Hematol.","year":"1995"},{"key":"2026012806224655900_R45","first-page":"23","article-title":"Rapid mobilization of intracellularly stored RANTES in response to interferon-\u03b3 in human eosinophils.","volume-title":"Blood","year":"1999"},{"key":"2026012806224655900_R46","first-page":"1047","article-title":"Human eosinophils secrete preformed, granule-stored interleukin-4 through distinct vesicular compartments.","volume-title":"Traffic","year":"2005"},{"key":"2026012806224655900_R47","first-page":"e26","article-title":"Differential secretion of cytokines.","volume-title":"Sci. STKE.","year":"2006"},{"key":"2026012806224655900_R48","first-page":"229","article-title":"Mechanisms of eosinophil secretion: large vesiculotubular carriers mediate transport and release of granule-derived cytokines and other proteins.","volume-title":"J. Leukocyte Biol.","year":"2008"},{"key":"2026012806224655900_R49","first-page":"105","article-title":"EliCell: a gel-phase dual antibody capture and detection assay to measure cytokine release from eosinophils.","volume-title":"J. Immunol. Methods","year":"2000"},{"key":"2026012806224655900_R50","first-page":"1553","article-title":"IL-7 induces myelopoiesis and erythropoiesis.","volume-title":"J. Immunol.","year":"2007"},{"key":"2026012806224655900_R51","first-page":"1453","article-title":"Functional participation of the IL-2 receptor \u03b3 chain in IL-7 receptor complexes.","volume-title":"Science","year":"1994"},{"key":"2026012806224655900_R52","first-page":"956","article-title":"Cytokine gene expression in human lung transplant recipients.","volume-title":"Transplantation","year":"1993"},{"key":"2026012806224655900_R53","first-page":"254","article-title":"Bronchoalveolar neutrophils, interferon gamma-inducible protein 10 and interleukin-7 in AIDS-associated tuberculosis.","volume-title":"Clin. Exp. Immunol.","year":"2007"},{"key":"2026012806224655900_R54","first-page":"1873","article-title":"Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines.","volume-title":"Blood","year":"2000"},{"key":"2026012806224655900_R55","first-page":"6298","article-title":"Interferon regulatory factor 1 (IRF-1) and IRF-2 distinctively up-regulate gene expression and production of interleukin-7 in human intestinal epithelial cells.","volume-title":"Mol. Cell Biol.","year":"2004"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/3\/1404\/62680415\/8449.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/182\/3\/1404\/62680415\/8449.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T11:23:12Z","timestamp":1769599392000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/182\/3\/1404\/8004481"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,2,1]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2009,2,1]]},"published-print":{"date-parts":[[2009,2,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.182.3.1404","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2009,2]]},"published":{"date-parts":[[2009,2,1]]}}}