{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:34:33Z","timestamp":1791401673871,"version":"4.3.3"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2010,4,1]],"date-time":"2010-04-01T00:00:00Z","timestamp":1270080000000},"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":[[2010,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>T lymphocytes of the Th2 type are central orchestrators of airway inflammation in asthma. The mechanisms that regulate their accumulation in the asthmatic airways remains poorly understood. We tested the hypothesis that CCR4, preferentially expressed on T lymphocytes of the Th2 type, plays a critical role in this process. We enumerated by flow cytometry the CCR4-expressing T cells from blood, induced sputum, and biopsy samples of patients with asthma and control subjects. We showed a positive correlation between the numbers of peripheral blood CCR4+ T cells and asthma severity, provided evidence of preferential accumulation of CCR4+ T cells in asthmatic airways, and demonstrated that CCR4+ but not CCR4\u2212 cells from patients with asthma produce Th2 cytokines. Explanted airway mucosal biopsy specimens, acquired by bronchoscopy from subjects with asthma, were challenged with allergen and the explant supernatants assayed for T cell chemotactic activity. Allergen-induced ex vivo production of the CCR4 ligand, CCL17 was raised in explants from patients with asthma when compared with healthy controls. Using chemotaxis assays, we showed that the T cell chemotactic activity generated by bronchial explants can be blocked with a selective CCR4 antagonist or by depleting CCR4+ cells from responder cells. These results provide evidence that CCR4 might play a role in allergen-driven Th2 cell accumulation in asthmatic airways. Targeting this chemokine receptor in patients with asthma might reduce Th2 cell-driven airway inflammation; therefore, CCR4 antagonists could be an effective new therapy for asthma. This study also provides wider proof of concept for using tissue explants to study immunomodulatory drugs for asthma.<\/jats:p>","DOI":"10.4049\/jimmunol.0901342","type":"journal-article","created":{"date-parts":[[2010,3,17]],"date-time":"2010-03-17T22:33:41Z","timestamp":1268865221000},"page":"4568-4574","source":"Crossref","is-referenced-by-count":88,"title":["Chemokine Receptor 4 Plays a Key Role in T Cell Recruitment into the Airways of Asthmatic Patients"],"prefix":"10.1093","volume":"184","author":[{"given":"Pandurangan","family":"Vijayanand","sequence":"first","affiliation":[{"name":"Inflammatory Cell Biology Group, Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton National Institute of Health Research Respiratory Biomedical Research Unit, Sir Henry Wellcome Laboratories, Southampton General Hospital , Southampton"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kesta","family":"Durkin","sequence":"additional","affiliation":[{"name":"Inflammatory Cell Biology Group, Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton National Institute of Health Research Respiratory Biomedical Research Unit, Sir Henry Wellcome Laboratories, Southampton General Hospital , Southampton"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Respiratory and Inflammation Centre of Excellence for Drug Discovery , GlaxoSmithKline, Stevenage,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaymin","family":"Morjaria","sequence":"additional","affiliation":[{"name":"Inflammatory Cell Biology Group, Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton National Institute of Health Research Respiratory Biomedical Research Unit, Sir Henry Wellcome Laboratories, Southampton General Hospital , Southampton"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Seumois","sequence":"additional","affiliation":[{"name":"Inflammatory Cell Biology Group, Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton National Institute of Health Research Respiratory Biomedical Research Unit, Sir Henry Wellcome Laboratories, Southampton General Hospital , Southampton"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl J","family":"Staples","sequence":"additional","affiliation":[{"name":"Inflammatory Cell Biology Group, Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton National Institute of Health Research Respiratory Biomedical Research Unit, Sir Henry Wellcome Laboratories, Southampton General Hospital , Southampton"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hall","sequence":"additional","affiliation":[{"name":"Respiratory and Inflammation Centre of Excellence for Drug Discovery , GlaxoSmithKline, Stevenage,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Bessant","sequence":"additional","affiliation":[{"name":"Respiratory and Inflammation Centre of Excellence for Drug Discovery , GlaxoSmithKline, Stevenage,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Bartholomew","sequence":"additional","affiliation":[{"name":"Respiratory and Inflammation Centre of Excellence for Drug Discovery , GlaxoSmithKline, Stevenage,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H","family":"Howarth","sequence":"additional","affiliation":[{"name":"Inflammatory Cell Biology Group, Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton National Institute of Health Research Respiratory Biomedical Research Unit, Sir Henry Wellcome Laboratories, Southampton General Hospital , Southampton"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S","family":"Friedmann","sequence":"additional","affiliation":[{"name":"Inflammatory Cell Biology Group, Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton National Institute of Health Research Respiratory Biomedical Research Unit, Sir Henry Wellcome Laboratories, Southampton General Hospital , Southampton"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratko","family":"Djukanovi\u0107","sequence":"additional","affiliation":[{"name":"Inflammatory Cell Biology Group, Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine, Southampton National Institute of Health Research Respiratory Biomedical Research Unit, Sir Henry Wellcome Laboratories, Southampton General Hospital , Southampton"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,4,15]]},"reference":[{"key":"2026012808073627300_r1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S0140-6736(06)69283-0","article-title":"Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys.","volume":"368","author":"Asher","year":"2006","journal-title":"Lancet"},{"key":"2026012808073627300_r2","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1056\/NEJM199201303260504","article-title":"Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma.","volume":"326","author":"Robinson","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"2026012808073627300_r3","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1067\/mai.2003.169","article-title":"The role of T lymphocytes in the pathogenesis of asthma.","volume":"111","author":"Larch\u00e9","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026012808073627300_r4","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1056\/NEJMoa064691","article-title":"Invariant natural killer T cells in asthma and chronic obstructive pulmonary disease.","volume":"356","author":"Vijayanand","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"2026012808073627300_r5","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1172\/JCI12655","article-title":"The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics.","volume":"107","author":"Panina-Bordignon","year":"2001","journal-title":"J. Clin. Invest."},{"key":"2026012808073627300_r6","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1084\/jem.187.6.875","article-title":"Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes.","volume":"187","author":"Sallusto","year":"1998","journal-title":"J. Exp. Med."},{"key":"2026012808073627300_r7","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1084\/jem.20040774","article-title":"Chemokine receptor expression identifies Pre-T helper (Th)1, Pre-Th2, and nonpolarized cells among human CD4+ central memory T cells.","volume":"200","author":"Rivino","year":"2004","journal-title":"J. Exp. Med."},{"key":"2026012808073627300_r8","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.4049\/jimmunol.162.3.1278","article-title":"Selective expression of a novel surface molecule by human Th2 cells in vivo.","volume":"162","author":"Nagata","year":"1999","journal-title":"J. Immunol."},{"key":"2026012808073627300_r9","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/23495","article-title":"The chemokine receptor CCR4 in vascu-lar recognition by cutaneous but not intestinal memory T cells.","volume":"400","author":"Campbell","year":"1999","journal-title":"Nature"},{"key":"2026012808073627300_r10","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1084\/jem.187.1.129","article-title":"Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s.","volume":"187","author":"Bonecchi","year":"1998","journal-title":"J. Exp. Med."},{"key":"2026012808073627300_r11","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4049\/jimmunol.166.1.103","article-title":"C-C chemokine receptor 4 expression defines a major subset of circulating nonintestinal memory T cells of both Th1 and Th2 potential.","volume":"166","author":"Andrew","year":"2001","journal-title":"J. Immunol."},{"key":"2026012808073627300_r12","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0161-5890(02)00013-5","article-title":"Cytokines and chemoattractants in allergic inflammation.","volume":"38","author":"Romagnani","year":"2002","journal-title":"Mol. Immunol."},{"key":"2026012808073627300_r13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/84298","article-title":"Chemokines: immunology\u2019s high impact factors.","volume":"2","author":"Mackay","year":"2001","journal-title":"Nat. Immunol."},{"key":"2026012808073627300_r14","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/84224","article-title":"Dancing to the tune of chemokines.","volume":"2","author":"Thelen","year":"2001","journal-title":"Nat. Immunol."},{"key":"2026012808073627300_r15","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.jaci.2003.08.012","article-title":"Release of both CCR4-active and CXCR3-active chemokines during human allergic pulmonary late-phase reactions.","volume":"112","author":"Bochner","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026012808073627300_r16","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1183\/09031936.04.00102504","article-title":"CCR4 ligands are up-regulated in the airways of atopic asthmatics after segmental allergen challenge.","volume":"23","author":"Pilette","year":"2004","journal-title":"Eur. Respir. J."},{"key":"2026012808073627300_r17","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1067\/mai.2002.130049","article-title":"Differential roles of IL-16 and CD28\/B7 costimulation in the generation of T-lymphocyte chemotactic activity in the bronchial mucosa of mild and moderate asthmatic individuals.","volume":"110","author":"Dent","year":"2002","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026012808073627300_r18","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1189\/jlb.0103030","article-title":"CCR4 blockade does not inhibit allergic airways inflammation.","volume":"74","author":"Conroy","year":"2003","journal-title":"J. Leukoc. Biol."},{"key":"2026012808073627300_r19","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.4049\/jimmunol.166.3.2055","article-title":"Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice.","volume":"166","author":"Kawasaki","year":"2001","journal-title":"J. Immunol."},{"key":"2026012808073627300_r20","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1084\/jem.191.2.265","article-title":"CC chemokine receptor (CCR)3\/eotaxin is followed by CCR4\/monocyte-derived chemokine in mediating pulmonary T helper lymphocyte type 2 recruitment after serial antigen challenge in vivo.","volume":"191","author":"Lloyd","year":"2000","journal-title":"J. Exp. Med."},{"key":"2026012808073627300_r21","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1096\/fj.02-0193fje","article-title":"Airway hyperresponsiveness, but not airway remodeling, is attenuated during chronic pulmonary allergic responses to Aspergillus in CCR4-\/- mice.","volume":"16","author":"Schuh","year":"2002","journal-title":"FASEB J."},{"key":"2026012808073627300_r22","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1034\/j.1398-9995.2003.00273.x","article-title":"The monocyte-derived chemokine is released in the bronchoalveolar lavage fluid of steady-state asthmatics.","volume":"58","author":"Lezcano-Meza","year":"2003","journal-title":"Allergy"},{"key":"2026012808073627300_r23","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1046\/j.1365-2222.2000.00088.x","article-title":"Global initiative for asthma (GINA) and its objectives.","volume":"30","author":"Bousquet","year":"2000","journal-title":"Clin. Exp. Allergy"},{"key":"2026012808073627300_r24","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1164\/ajrccm.163.5.2101039","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. NHLBI\/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop summary.","volume":"163","author":"Pauwels","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026012808073627300_r25","first-page":"51s","article-title":"Standardised methodology of sputum induction and processing. Future directions.","volume":"37","author":"Vignola","year":"2002","journal-title":"Eur. Respir. J. Suppl."},{"key":"2026012808073627300_r26","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1164\/ajrccm\/143.4_Pt_1.772","article-title":"The safety aspects of fiberoptic bronchoscopy, bronchoalveolar lavage, and endobronchial biopsy in asthma.","volume":"143","author":"Djukanovi\u0107","year":"1991","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026012808073627300_r27","doi-asserted-by":"crossref","first-page":"412","DOI":"10.4049\/jimmunol.164.1.412","article-title":"Role of B7-CD28\/CTLA-4 costimulation and NF-kappa B in allergen-induced T cell chemotaxis by IL-16 and RANTES.","volume":"164","author":"Hidi","year":"2000","journal-title":"J. Immunol."},{"key":"2026012808073627300_r28","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1046\/j.1365-2745.2002.01383.x","article-title":"Characterization of chemokine receptor expression and cytokine production in circulating CD4+ T cells from patients with atopic dermatitis: up-regulation of C-C chemokine receptor 4 in atopic dermatitis.","volume":"32","author":"Okazaki","year":"2002","journal-title":"Clin. Exp. Allergy"},{"key":"2026012808073627300_r29","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1164\/ajrccm.164.5.2008132","article-title":"Effects of oral steroids on blood CXCR3+ and CCR4+ T cells in patients with bronchial asthma.","volume":"164","author":"Kurashima","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026012808073627300_r30","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nri2254","article-title":"Immunology of asthma and chronic obstructive pulmonary disease.","volume":"8","author":"Barnes","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2026012808073627300_r31","doi-asserted-by":"crossref","first-page":"4488","DOI":"10.4049\/jimmunol.177.7.4488","article-title":"The majority of human peripheral blood CD4+CD25highFoxp3+ regulatory T cells bear functional skin-homing receptors.","volume":"177","author":"Hirahara","year":"2006","journal-title":"J. Immunol."},{"key":"2026012808073627300_r32","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/S0140-6736(04)15592-X","article-title":"Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease.","volume":"363","author":"Ling","year":"2004","journal-title":"Lancet"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/8\/4568\/62711813\/ji_0901342.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/184\/8\/4568\/62711813\/ji_0901342.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T13:07:47Z","timestamp":1769605667000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/184\/8\/4568\/8013267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,4]]},"references-count":32,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2010,4,15]]},"published-print":{"date-parts":[[2010,4,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.0901342","relation":{},"ISSN":["1550-6606","0022-1767"],"issn-type":[{"value":"1550-6606","type":"electronic"},{"value":"0022-1767","type":"print"}],"subject":[],"published-other":{"date-parts":[[2010,4]]},"published":{"date-parts":[[2010,4]]}}}