{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:13:27Z","timestamp":1791242007490,"version":"4.1.0"},"reference-count":47,"publisher":"Rockefeller University Press","issue":"9","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,5,7]]},"abstract":"<jats:p>Antigen-specific CD4 T helper type 2 (Th2) cells play a pivotal role in the induction of allergic asthma, but the mechanisms regulating their recruitment into the airways are unknown. Signal transducer and activator of transcription factor (Stat)6 is a transcription factor essential for Th2 cell differentiation. Here we show that Stat6 also controls Th2 cell recruitment and effector function in allergic inflammation in vivo. To isolate the role of Stat6 in regulating Th2 cell trafficking and effector function from its role in Th2 cell differentiation, we used a murine model of asthma in which in vitro\u2013differentiated Stat6+\/+ antigen-specific Th2 cells were adoptively transferred into naive Stat6\u2212\/\u2212 and Stat6+\/+ mice followed by aerosol antigen challenge. We found that all of the features of asthma, including Th2 cell accumulation, Th2 and eosinophil-active chemokine production, and airway eosinophilia, mucus production, and hyperresponsiveness seen in Stat6+\/+ mice, were dramatically absent in Stat6\u2212\/\u2212 mice that received Stat6+\/+ antigen-specific Th2 cells. Our findings establish Stat6 as essential for Th2 cell trafficking and effector function and suggest that interruption of Stat6 signaling in resident cells of the lung is a novel approach to asthma therapy.<\/jats:p>","DOI":"10.1084\/jem.193.9.1087","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1087-1096","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":133,"title":["Signal Transducer and Activator of Transcription 6 Controls Chemokine Production and T Helper Cell Type 2 Cell Trafficking in Allergic Pulmonary Inflammation"],"prefix":"10.1084","volume":"193","author":[{"given":"Anuja","family":"Mathew","sequence":"first","affiliation":[{"name":"aCenter for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"MacLean","sequence":"additional","affiliation":[{"name":"aCenter for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot","family":"DeHaan","sequence":"additional","affiliation":[{"name":"aCenter for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Tager","sequence":"additional","affiliation":[{"name":"aCenter for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis H.Y.","family":"Green","sequence":"additional","affiliation":[{"name":"bDepartment of Pathology, University of Calgary, Calgary, Alberta, Canada T2N 1N4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Luster","sequence":"additional","affiliation":[{"name":"aCenter for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2001,5,7]]},"reference":[{"key":"2023072509453708700_R1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev.immunol.17.1.255","article-title":"Immunologic basis of antigen-induced airway hyperresponsiveness","volume":"17","author":"Wills-Karp","year":"1999","journal-title":"Annu. Rev. Immunol."},{"key":"2023072509453708700_R2","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1002\/eji.1830230707","article-title":"Allergen exposure induces the activation of allergen-specific Th2 cells in the airway mucosa of patients with allergic respiratory disorders","volume":"23","author":"Del Prete","year":"1993","journal-title":"Eur. J. Immunol"},{"key":"2023072509453708700_R3","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. Eng. J. Med."},{"key":"2023072509453708700_R4","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1164\/ajrccm\/146.1.109","article-title":"Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage","volume":"146","author":"Walker","year":"1992","journal-title":"Am. Rev. Respir. Dis."},{"key":"2023072509453708700_R5","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1165\/ajrcmb.12.3.7873190","article-title":"Allergen-induced airway inflammation and bronchial responsiveness in wildtype and IL-4 deficient mice","volume":"12","author":"Bruselle","year":"1995","journal-title":"Am. J. Respir. Cell Biol."},{"key":"2023072509453708700_R6","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1084\/jem.183.1.195","article-title":"Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model","volume":"183","author":"Foster","year":"1996","journal-title":"J. Exp. Med."},{"key":"2023072509453708700_R7","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1126\/science.282.5397.2261","article-title":"Requirement for IL-13 independently of IL-4 in experimental asthma","volume":"282","author":"Grunig","year":"1998","journal-title":"Science."},{"key":"2023072509453708700_R8","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1126\/science.282.5397.2258","article-title":"IL-13a central mediator of allergic asthma","volume":"282","author":"Wills-Karp","year":"1998","journal-title":"Science."},{"key":"2023072509453708700_R9","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1084\/jem.186.10.1737","article-title":"Induction of airway mucus production by T helper 2 (Th2) cellsa critical role for interleukin 4 in cell recruitment but not mucus production","volume":"186","author":"Cohn","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072509453708700_R10","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.4049\/jimmunol.161.6.3128","article-title":"Th2-induced eotaxin expression and eosinophilia coexist with Th1 responses at the effector stage of lung inflammation","volume":"161","author":"Li","year":"1998","journal-title":"J. Immunol."},{"key":"2023072509453708700_R11","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.4049\/jimmunol.160.3.1378","article-title":"Induction of pulmonary allergic responses by antigen-specific Th2 cells","volume":"160","author":"Li","year":"1998","journal-title":"J. Immunol."},{"key":"2023072509453708700_R12","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1038\/sj.onc.1203485","article-title":"The biology of Stat4 and Stat6","volume":"19","author":"Wurster","year":"2000","journal-title":"Oncogene."},{"key":"2023072509453708700_R13","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S1074-7613(00)80439-2","article-title":"Stat6 is required for mediating responses to IL-4 and for development of Th2 cells","volume":"4","author":"Kaplan","year":"1996","journal-title":"Immunity."},{"key":"2023072509453708700_R14","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/380627a0","article-title":"Essential role of Stat6 in IL-4 signaling","volume":"380","author":"Takeda","year":"1996","journal-title":"Nature."},{"key":"2023072509453708700_R15","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1146\/annurev.immunol.16.1.293","article-title":"JAKS and STATsbiological implications","volume":"16","author":"Leonard","year":"1998","journal-title":"Annu. Rev. Immunol."},{"key":"2023072509453708700_R16","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1084\/jem.187.9.1537","article-title":"Abrogation of bronchial eosinophilic inflammation and airway hyperreactivity in signal transducers and activators of transcription (STAT)6-deficient mice","volume":"187","author":"Akimoto","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072509453708700_R17","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1084\/jem.187.6.939","article-title":"Signal transducer and activator of transcription factor 6 (Stat6)-deficient mice are protected from antigen-induced airway hyperresponsiveness and mucus production","volume":"187","author":"Kuperman","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072509453708700_R18","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1164\/ajrccm.160.4.9809065","article-title":"The failure of STAT6-deficient mice to develop airway eosinophilia and airway hyperresponsiveness is overcome by interleukin-5","volume":"160","author":"Tomkinson","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2023072509453708700_R19","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1084\/jem.184.4.1461","article-title":"T cell\u2013dependent regulation of eotaxin in antigen-induced pulmonary eosinophilia","volume":"184","author":"MacLean","year":"1996","journal-title":"J. Exp. Med."},{"key":"2023072509453708700_R20","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1172\/JCI119145","article-title":"Chemokine receptor usage by human eosinophilsthe importance of CCR3 demonstrated using an antagonistic monoclonal antibody","volume":"99","author":"Heath","year":"1997","journal-title":"J. Clin. Invest."},{"key":"2023072509453708700_R21","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/S0167-5699(98)01346-2","article-title":"Chemokines and chemokine receptors in T-cell priming and Th1\/Th2-mediated responses","volume":"19","author":"Sallusto","year":"1998","journal-title":"Immunol. Today."},{"key":"2023072509453708700_R22","doi-asserted-by":"crossref","first-page":"10","DOI":"10.4049\/jimmunol.165.1.10","article-title":"Cutting edgedifferential expression of chemokines in Th1 and Th2 cells is dependent on Stat6 but not Stat4","volume":"165","author":"Zhang","year":"2000","journal-title":"J. Immunol."},{"key":"2023072509453708700_R23","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.4049\/jimmunol.141.5.1563","article-title":"The expression and regulation of a potential lymphokine gene (TCA3) in CD4 and CD8 T cell clones","volume":"141","author":"Wilson","year":"1988","journal-title":"J. Immunol."},{"key":"2023072509453708700_R24","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/0091-6749(90)90151-S","article-title":"The eosinophil and bronchial asthmacurrent understanding","volume":"85","author":"Gleich","year":"1990","journal-title":"J. Allergy Clin. Immunol."},{"key":"2023072509453708700_R25","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1056\/NEJM199104183241607","article-title":"The immunobiology of eosinophils","volume":"324","author":"Weller","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"2023072509453708700_R26","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1182\/blood.V79.12.3101.bloodjournal79123101","article-title":"Interleukin-5, eosinophils, and disease","volume":"79","author":"Sanderson","year":"1992","journal-title":"Blood."},{"key":"2023072509453708700_R27","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1165\/ajrcmb.16.4.9115759","article-title":"A novel role for murine IL-4 in vivoinduction of MUC5AC gene expression and mucin hypersecretion","volume":"16","author":"Temann","year":"1997","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2023072509453708700_R28","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1084\/jem.167.2.598","article-title":"Interleukin-4 induces cultured monocytes\/macrophages to form multinucleated giant cells","volume":"167","author":"McInnes","year":"1988","journal-title":"J. Exp. Med."},{"key":"2023072509453708700_R29","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1172\/JCI5909","article-title":"Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production","volume":"103","author":"Zhu","year":"1999","journal-title":"J. Clin. Invest."},{"key":"2023072509453708700_R30","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.1084\/jem.185.12.2143","article-title":"IL-5 expression in the lung epithelium of transgenic mice leads to pulmonary changes pathognomonic of asthma","volume":"185","author":"Lee","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072509453708700_R31","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0167-5699(00)01590-5","article-title":"Localization of Th-cell subsets in inflammationdifferential thresholds for extravasation of Th1 and Th2 cells","volume":"21","author":"D'Ambrosio","year":"2000","journal-title":"Immunol. Today."},{"key":"2023072509453708700_R32","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/385081a0","article-title":"P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissues","volume":"385","author":"Austrup","year":"1997","journal-title":"Nature."},{"key":"2023072509453708700_R33","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1084\/jem.185.3.573","article-title":"P-selectin glycoprotein ligand-1 (PSGL-1) on T helper 1 but not on T helper 2 cells binds to P-selectin and supports migration into inflamed skin","volume":"185","author":"Borges","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072509453708700_R34","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1084\/jem.189.11.1765","article-title":"Acquisition of selectin binding and peripheral homing properties by CD4+ and CD8+ T cells","volume":"189","author":"Xie","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023072509453708700_R35","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1172\/JCI118829","article-title":"IL-4 and IL-13 activate JAK2 tyrosine and Stat6 in cultured human vascular endothelial cells through a common pathway that does not involve the \u03b3-c chain","volume":"98","author":"Palmer-Crocker","year":"1996","journal-title":"J. Clin. Invest."},{"key":"2023072509453708700_R36","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1084\/jem.191.10.1755","article-title":"A key role for CC chemokine receptor 4 in lipopolysaccharide-induced endotoxic shock","volume":"191","author":"Chvatchko","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023072509453708700_R37","doi-asserted-by":"crossref","first-page":"403","DOI":"10.4049\/jimmunol.163.1.403","article-title":"Mouse monocyte-derived chemokine is involved in airway hyperreactivity and lung inflammation","volume":"163","author":"Gonzalo","year":"1999","journal-title":"J. Immunol."},{"key":"2023072509453708700_R38","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":"2023072509453708700_R39","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1084\/jem.185.4.785","article-title":"Targeted disruption of the chemokine eotaxin only partially reduces antigen induced tissue eosinophilia","volume":"185","author":"Rothenberg","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072509453708700_R40","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/nm0496-449","article-title":"Human eotaxin is specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia","volume":"4","author":"Garcia-Zepeda","year":"1996","journal-title":"Nat. Med."},{"key":"2023072509453708700_R41","doi-asserted-by":"crossref","first-page":"60","DOI":"10.4049\/jimmunol.160.1.60","article-title":"IL-4 induces eotaxina possible mechanism of selective eosinophil recruitment in helminth infection and atopy","volume":"160","author":"Mochizuki","year":"1998","journal-title":"J. Immunol."},{"key":"2023072509453708700_R42","doi-asserted-by":"crossref","first-page":"5624","DOI":"10.4049\/jimmunol.163.10.5624","article-title":"Differential regulation of epithelial-derived C-C chemokine expression by IL-4 and the glucocorticoid budesonide","volume":"163","author":"Stellato","year":"1999","journal-title":"J. Immunol."},{"key":"2023072509453708700_R43","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.4049\/jimmunol.162.5.2477","article-title":"Effects of Th2 cytokines on chemokine expression in the lungIL-13 induces eotaxin expression by airway epithelial cells","volume":"162","author":"Li","year":"1999","journal-title":"J. Immunol."},{"key":"2023072509453708700_R44","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.4049\/jimmunol.163.3.1602","article-title":"A novel human CC chemokine eotaxin-3, which is expressed in IL-4 stimulated vascular endothelial cells, exhibits potent activity toward eosinophils","volume":"163","author":"Shinkai","year":"1999","journal-title":"J. Immunol."},{"key":"2023072509453708700_R45","doi-asserted-by":"crossref","first-page":"5839","DOI":"10.4049\/jimmunol.165.10.5839","article-title":"Murine eotaxin-2a constitutive eosinophil chemokine induced by allergen challenge and IL-4 overexpression","volume":"165","author":"Zimmermann","year":"2000","journal-title":"J. Immunol."},{"key":"2023072509453708700_R46","doi-asserted-by":"crossref","first-page":"6876","DOI":"10.4049\/jimmunol.163.12.6876","article-title":"Activation of eotaxin gene transcription by NF-\u03baB and STAT6 in human airway epithelial cells","volume":"163","author":"Matsukura","year":"1999","journal-title":"J. Immunol."},{"key":"2023072509453708700_R47","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.4049\/jimmunol.165.4.2205","article-title":"Inducible expression of a Th2-type CC chemokine thymus- and activation-regulated chemokine by human bronchial epithelial cells","volume":"165","author":"Sekiya","year":"2000","journal-title":"J. Immunol."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/193\/9\/1087\/1702369\/010062.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/193\/9\/1087\/1702369\/010062.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T10:55:39Z","timestamp":1690282539000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/193\/9\/1087\/39368\/Signal-Transducer-and-Activator-of-Transcription-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,5,7]]},"references-count":47,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2001,5,7]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.193.9.1087","relation":{},"ISSN":["0022-1007","1540-9538"],"issn-type":[{"value":"0022-1007","type":"print"},{"value":"1540-9538","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,5,7]]}}}