{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:24:28Z","timestamp":1790745868480,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:00:00Z","timestamp":1594684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology in Japan","doi-asserted-by":"publisher","award":["18K08410"],"award-info":[{"award-number":["18K08410"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,12]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Systemic sclerosis (SSc) is a T helper type 2 (Th2)-associated autoimmune disease characterized by vasculopathy and fibrosis. Efficacy of B cell depletion therapy underscores antibody-independent functions of B cells in SSc. A recent study showed that the Th2 cytokine interleukin (IL)-4 induces granulocyte\u2013macrophage colony-stimulating factor (GM-CSF)-producing effector B cells (GM-Beffs) in humans. In this study, we sought to elucidate the generation mechanism of GM-Beffs and also determine a role of this subset in SSc. Among Th-associated cytokines, IL-4 most significantly facilitated the generation of GM-Beffs within memory B cells in healthy controls (HCs). In addition, the profibrotic cytokine transforming growth factor (TGF)-\u03b2 further potentiated IL-4- and IL-13-induced GM-Beffs. Of note, tofacitinib, a Janus kinase (JAK) inhibitor, inhibited the expression of GM-CSF mRNA and protein in memory B cells induced by IL-4, but not by TGF-\u03b2. GM-Beffs were enriched within CD20+CD30+CD38\u2212\/low cells, a distinct population from plasmablasts, suggesting that GM-Beffs exert antibody-independent functions. GM-Beffs were also enriched in a CD30+ fraction of freshly isolated B cells. GM-Beffs generated under Th2 conditions facilitated the differentiation from CD14+ monocytes to DC-SIGN+CD1a+CD14\u2212CD86+ cells, which significantly promoted the proliferation of naive T cells. CD30+ GM-Beffs were more pronounced in patients with SSc than in HCs. A subpopulation of SSc patients with the diffuse type and concomitant interstitial lung disease exhibited high numbers of GM-Beffs. Together, these findings suggest that human GM-Beffs are enriched in a CD30+ B cell subset and play a role in the pathogenesis of SSc.<\/jats:p>","DOI":"10.1111\/cei.13477","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T12:40:30Z","timestamp":1592224830000},"page":"233-243","source":"Crossref","is-referenced-by-count":27,"title":["Generation of a novel CD30+ B cell subset producing GM-CSF and its possible link to the pathogenesis of systemic sclerosis"],"prefix":"10.1093","volume":"201","author":[{"given":"K","family":"Higashioka","sequence":"first","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University , Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Kikushige","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University , Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Ayano","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University , Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Kimoto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kyushu University Beppu Hospital, Tsurumihara , Beppu, Oita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Mitoma","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University , Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Kikukawa","sequence":"additional","affiliation":[{"name":"Department of Medical Education, Faculty of Medical Sciences, Kyushu University , Fukuoka, 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