{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:51:59Z","timestamp":1790373119892,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T00:00:00Z","timestamp":1535500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7172178"],"award-info":[{"award-number":["7172178"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003345","name":"Chinese Academy of Meteorological Sciences","doi-asserted-by":"publisher","award":["2017\u201012M\u20103\u2010001"],"award-info":[{"award-number":["2017\u201012M\u20103\u2010001"]}],"id":[{"id":"10.13039\/501100003345","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81373190"],"award-info":[{"award-number":["81373190"]}],"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":["81571587"],"award-info":[{"award-number":["81571587"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7172178"],"award-info":[{"award-number":["7172178"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2018,11]]},"abstract":"Objective<\/jats:title>To determine the number and function of follicular helper T (Tfh) cell subsets in IgG4\u2010related disease (IgG4\u2010RD<\/jats:styled-content>).<\/jats:p><\/jats:sec>Methods<\/jats:title>Mononuclear cells from the peripheral blood and involved tissue of patients with IgG4\u2010RD<\/jats:styled-content> were assessed for Tfh cells and their subsets, and levels of B cell lymphoma 6 (Bcl\u20106), B lymphocyte\u2013induced maturation protein 1 (BLIMP<\/jats:styled-content>\u20101), and interleukin\u201021 (IL<\/jats:styled-content>\u201021) messenger RNA<\/jats:styled-content> (mRNA<\/jats:styled-content>). Immunohistochemical and immunofluorescence techniques were used to assess the involved tissue of patients to determine the location of IL<\/jats:styled-content>\u201021, Bcl\u20106, and CD<\/jats:styled-content>4+CXCR<\/jats:styled-content>5+ Tfh cells. Furthermore, the ability of circulating Tfh (cT<\/jats:styled-content>fh) cell subsets to induce B cell proliferation, apoptosis, and differentiation and to produce IgG4 was explored in cell cocultures in vitro.<\/jats:p><\/jats:sec>Results<\/jats:title>Frequencies of cT<\/jats:styled-content>fh cells were significantly increased in the peripheral blood of patients with IgG4\u2010RD<\/jats:styled-content>, and even higher frequencies were observed in the involved tissue. Percentages of programmed cell death protein 1 in CD<\/jats:styled-content>4+CXCR<\/jats:styled-content>5+ICOS<\/jats:styled-content>+ cT<\/jats:styled-content>fh cells were positively correlated with the serum levels of IgG and IgG4, IgG4:IgG ratio, number of involved organs, and frequency of CD<\/jats:styled-content>19+CD<\/jats:styled-content>24\u2212CD<\/jats:styled-content>38high<\/jats:sup> plasmablasts\/plasma cells. Levels of BLIMP<\/jats:styled-content>\u20101 and IL<\/jats:styled-content>\u201021 mRNA<\/jats:styled-content> in peripheral CD<\/jats:styled-content>4+ T cells were increased in patients with IgG4\u2010RD<\/jats:styled-content> compared to healthy controls, and this was correlated with the levels of serum IgG4. Moreover, in the involved tissue, Bcl\u20106, IL<\/jats:styled-content>\u201021, and Tfh cells were highly expressed. Compared to cT<\/jats:styled-content>fh cells from healthy controls, cT<\/jats:styled-content>fh cells from patients with IgG4\u2010RD<\/jats:styled-content> could facilitate B cell proliferation and inhibit B cell apoptosis more efficiently, and enhanced the differentiation of naive B cells into switched memory B cells and plasmablasts\/plasma cells, with a resultant increase in the secretion of IgG4. Notably, the cTfh1 and cTfh2 cell subsets were the most effective at providing B cell help.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Tfh cell subsets are expanded in IgG4\u2010RD<\/jats:styled-content> and may play pivotal roles in the pathogenesis of the disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40556","type":"journal-article","created":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T04:30:30Z","timestamp":1526877030000},"page":"1853-1865","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Aberrant Expansion and Function of Follicular Helper T Cell Subsets in IgG4\u2010Related Disease"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7142-8851","authenticated-orcid":false,"given":"Yu","family":"Chen","sequence":"first","affiliation":[{"name":"Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China and Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Hebei Provincial General Hospital Shijiazhuang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxian","family":"Yang","sequence":"additional","affiliation":[{"name":"Children's Hospital Capital Institute of Pediatrics Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruie","family":"Feng","sequence":"additional","affiliation":[{"name":"Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyi","family":"Peng","sequence":"additional","affiliation":[{"name":"Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8775-1699","authenticated-orcid":false,"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengchun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E.","family":"Lipsky","sequence":"additional","affiliation":[{"name":"RILITE Research Institute Charlottesville Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2012.18"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2016.06.010"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20141432"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1877"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091777"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175870"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.12.012"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.06.002"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.10.004"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431X20165209"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket434"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39132"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1104650"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205233"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4571"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1231-2"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.3109\/s10165-011-0571-z"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2013.55"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39209"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-041015-055605"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.025"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.03.003"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-016-1064-4"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-016-0268-3"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005191"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep26494"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.031"}],"container-title":["Arthritis & Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.40556","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.40556","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T11:30:25Z","timestamp":1759923025000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.40556"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,29]]},"references-count":27,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1002\/art.40556"],"URL":"https:\/\/doi.org\/10.1002\/art.40556","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,29]]},"assertion":[{"value":"2017-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}