{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:23:26Z","timestamp":1791933806505,"version":"4.3.4"},"reference-count":49,"publisher":"European Respiratory Society (ERS)","issue":"5","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81925001"],"award-info":[{"award-number":["81925001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170052"],"award-info":[{"award-number":["82170052"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82330070"],"award-info":[{"award-number":["82330070"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003395","name":"Shanghai Municipal Education Commission","doi-asserted-by":"publisher","award":["202101070007-E00097"],"award-info":[{"award-number":["202101070007-E00097"]}],"id":[{"id":"10.13039\/501100003395","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovative research team of high-level local universities in Shanghai and Innovative team of Shanghai Pulmonary Hospital"},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["21DZ2201800"],"award-info":[{"award-number":["21DZ2201800"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2024,3,7]]},"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) and 17 (Th17) cells, regulatory T-cells (Treg) and interleukin (IL)-21<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T-cells in total or sorted subsets of peripheral blood mononuclear cells and ABPA bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing of subsets of CD4<jats:sup>+<\/jats:sup>T-cells was done in exacerbated ABPA patients and healthy controls. Antibodies of T-\/B-cell co-cultures<jats:italic>in vitro<\/jats:italic>were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ABPA patients had increased Th2 cells, similar numbers of Treg cells and decreased circulating Th1 and Th17 cells. IL-5<jats:sup>+<\/jats:sup>IL-13<jats:sup>+<\/jats:sup>IL-21<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T-cells were rarely detected in healthy controls, but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5<jats:sup>+<\/jats:sup>IL-13<jats:sup>+<\/jats:sup>IL-21<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup>T-cells were mainly peripheral T-helper (Tph) cells (PD-1<jats:sup>+<\/jats:sup>CXCR5<jats:sup>\u2212<\/jats:sup>), which also presented in the BALF of ABPA patients. The proportions of circulating Tph cells were similar among ABPA patients, asthma patients and healthy controls, while IL-5<jats:sup>+<\/jats:sup>IL-13<jats:sup>+<\/jats:sup>IL-21<jats:sup>+<\/jats:sup>Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T-helper cells. When co-cultured<jats:italic>in vitro<\/jats:italic>, Tph cells of ABPA patients induced the differentiation of autologous B-cells into plasmablasts and significantly enhanced the production of IgE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.<\/jats:p><\/jats:sec>","DOI":"10.1183\/13993003.00386-2024","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T16:45:11Z","timestamp":1711039511000},"page":"2400386","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Th2-skewed peripheral T-helper cells drive B-cells in allergic bronchopulmonary aspergillosis"],"prefix":"10.1183","volume":"63","author":[{"given":"Rong-Guang","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Fan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Wen","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Yan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le-Le","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Sha","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cai-Qi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Xiong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Ming","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8039-8973","authenticated-orcid":false,"given":"Jin-Fu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"2024102103243974000_63.5.2400386.1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12141"},{"key":"2024102103243974000_63.5.2400386.2","doi-asserted-by":"publisher","DOI":"10.4103\/ijmr.IJMR_1187_19"},{"key":"2024102103243974000_63.5.2400386.3","doi-asserted-by":"publisher","DOI":"10.1111\/crj.13111"},{"key":"2024102103243974000_63.5.2400386.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0112-4"},{"key":"2024102103243974000_63.5.2400386.5","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.118"},{"key":"2024102103243974000_63.5.2400386.6","doi-asserted-by":"publisher","DOI":"10.1016\/J.IMMUNI.2019.03.022"},{"key":"2024102103243974000_63.5.2400386.7","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.immuni.2019.03.018","article-title":"The cytokines of asthma","volume":"50","author":"Lambrecht","year":"2019","journal-title":"Immunity"},{"key":"2024102103243974000_63.5.2400386.8","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101283"},{"key":"2024102103243974000_63.5.2400386.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.08.017"},{"key":"2024102103243974000_63.5.2400386.10","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1984"},{"key":"2024102103243974000_63.5.2400386.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.09.048"},{"key":"2024102103243974000_63.5.2400386.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.08.007"},{"key":"2024102103243974000_63.5.2400386.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.04.021"},{"key":"2024102103243974000_63.5.2400386.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.11.020"},{"key":"2024102103243974000_63.5.2400386.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.04.011"},{"key":"2024102103243974000_63.5.2400386.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1809329116"},{"key":"2024102103243974000_63.5.2400386.17","doi-asserted-by":"publisher","DOI":"10.1038\/nri3803"},{"key":"2024102103243974000_63.5.2400386.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.07.015"},{"key":"2024102103243974000_63.5.2400386.19","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20180927"},{"key":"2024102103243974000_63.5.2400386.20","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw6433"},{"key":"2024102103243974000_63.5.2400386.21","doi-asserted-by":"publisher","DOI":"10.1038\/nature20810"},{"key":"2024102103243974000_63.5.2400386.22","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0011-2022"},{"key":"2024102103243974000_63.5.2400386.23","unstructured":"Global Initiative for Asthma (GINA) . Pocket Guide for Asthma Management and Prevention (for Adults and Children Older than 5 Years). 2019. https:\/\/ginasthma.org\/wp-content\/uploads\/2019\/04\/GINA-2019-main-Pocket-Guide-wms.pdf"},{"key":"2024102103243974000_63.5.2400386.24","doi-asserted-by":"crossref","first-page":"939127","DOI":"10.3389\/fimmu.2022.939127","article-title":"Clinical and immunological characteristics of Aspergillus fumigatus-sensitized asthma and allergic bronchopulmonary aspergillosis","volume":"13","author":"Chen","year":"2022","journal-title":"Front Immunol"},{"key":"2024102103243974000_63.5.2400386.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2021.03.001"},{"key":"2024102103243974000_63.5.2400386.26","doi-asserted-by":"crossref","first-page":"111895","DOI":"10.1016\/j.celrep.2022.111895","article-title":"PD-1highCXCR5\u2212CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection","volume":"42","author":"Asashima","year":"2023","journal-title":"Cell Rep"},{"key":"2024102103243974000_63.5.2400386.27","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13069"},{"key":"2024102103243974000_63.5.2400386.28","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1172\/JCI125917","article-title":"Single-cell RNA sequencing identifies inflammatory tissue T cells in eosinophilic esophagitis","volume":"129","author":"Wen","year":"2019","journal-title":"J Clin Invest"},{"key":"2024102103243974000_63.5.2400386.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.05.033"},{"key":"2024102103243974000_63.5.2400386.30","doi-asserted-by":"crossref","first-page":"eabi9768","DOI":"10.1126\/sciimmunol.abi9768","article-title":"An IL-9-pulmonary macrophage axis defines the allergic lung inflammatory environment","volume":"7","author":"Fu","year":"2022","journal-title":"Sci Immunol"},{"key":"2024102103243974000_63.5.2400386.31","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(00)90185-4"},{"key":"2024102103243974000_63.5.2400386.32","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/j.jaci.2019.06.011","article-title":"Thymic stromal lymphopoietin epigenetically upregulates Fc receptor \u03b3 subunit-related receptors on antigen-presenting cells and induces TH2\/TH17 polarization through dectin-2","volume":"144","author":"Liang","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"2024102103243974000_63.5.2400386.33","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jdsr.2019.07.002","article-title":"Obesity-induced asthma: role of free fatty acid receptors","volume":"55","author":"Mizuta","year":"2019","journal-title":"Jpn Dent Sci Rev"},{"key":"2024102103243974000_63.5.2400386.34","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0140-6736(22)02037-2","article-title":"An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: a multicentre, double-blind, placebo-controlled phase 2b study","volume":"401","author":"Guttman-Yassky","year":"2023","journal-title":"Lancet"},{"key":"2024102103243974000_63.5.2400386.35","doi-asserted-by":"publisher","DOI":"10.1378\/chest.11-1730"},{"key":"2024102103243974000_63.5.2400386.36","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-19-0934"},{"key":"2024102103243974000_63.5.2400386.37","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1901350"},{"key":"2024102103243974000_63.5.2400386.38","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(02)00210-9"},{"key":"2024102103243974000_63.5.2400386.39","doi-asserted-by":"crossref","first-page":"eabf5314","DOI":"10.1126\/sciimmunol.abf5314","article-title":"Lung-resident memory B cells established after pulmonary influenza infection display distinct transcriptional and phenotypic profiles","volume":"7","author":"Tan","year":"2022","journal-title":"Sci Immunol"},{"key":"2024102103243974000_63.5.2400386.40","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/cmi.2017.107","article-title":"The unique structural and functional features of CXCL12","volume":"15","author":"Janssens","year":"2018","journal-title":"Cell Mol Immunol"},{"key":"2024102103243974000_63.5.2400386.41","first-page":"4558159","article-title":"CXC chemokines in the pathogenesis of pulmonary disease and pharmacological relevance","volume":"2022","author":"Komolafe","year":"2022","journal-title":"Int J Inflam"},{"key":"2024102103243974000_63.5.2400386.42","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-00974-6"},{"key":"2024102103243974000_63.5.2400386.43","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1016\/j.jaci.2015.09.036","article-title":"Myeloid differentiation protein 2 facilitates pollen- and cat dander-induced innate and allergic airway inflammation","volume":"137","author":"Hosoki","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"2024102103243974000_63.5.2400386.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.041"},{"key":"2024102103243974000_63.5.2400386.45","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/S2213-8587(21)00019-X","article-title":"Anti-interleukin-21 antibody and liraglutide for the preservation of \u03b2-cell function in adults with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled, phase 2 trial","volume":"9","author":"von Herrath","year":"2021","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2024102103243974000_63.5.2400386.46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00631.x"},{"key":"2024102103243974000_63.5.2400386.47","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12740"},{"key":"2024102103243974000_63.5.2400386.48","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.apsb.2019.08.010","article-title":"Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity","volume":"10","author":"Fu","year":"2020","journal-title":"Acta Pharm Sin B"},{"key":"2024102103243974000_63.5.2400386.49","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw6433"}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.00386-2024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T07:19:53Z","timestamp":1740381593000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.00386-2024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,21]]},"references-count":49,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5,16]]},"published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1183\/13993003.00386-2024"],"URL":"https:\/\/doi.org\/10.1183\/13993003.00386-2024","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,21]]}}}