{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:01:01Z","timestamp":1790740861960,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,5,2]],"date-time":"2020-05-02T00:00:00Z","timestamp":1588377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) grant funded by the Korean government","award":["NRF-2018R1A2B3002179"],"award-info":[{"award-number":["NRF-2018R1A2B3002179"]}]},{"name":"Yonsei University Research Fund","award":["2019-22-0193"],"award-info":[{"award-number":["2019-22-0193"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phospholipase D1 (PLD1) plays a crucial role in various inflammatory and autoimmune diseases. Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease. However, the role of PLD1 in the pathogenesis of RA remains unknown. Here, we first investigated the role and effects of PLD1 in collagen-induced arthritis (CIA) and found that genetic and pharmacological inhibition of PLD1 in DBA1\/J mice with CIA reduced the incidence of CIA, decreased the clinical score, and abrogated disease symptoms including infiltration of leukocytes, synovial inflammation, bone erosion, and cartilage destruction. Moreover, ablation and inhibition of PLD1 suppressed the production of type II collagen-specific IgG2a autoantibody and proinflammatory cytokines, accompanied by an increase in the regulatory T (Treg) cell population and a decrease in the Th17 cell population in CIA mice. The PLD1 inhibitor also promoted differentiation of Treg cells and suppressed differentiation of Th17 cells in vitro. Furthermore, the PLD1 inhibitor attenuated pathologic bone destruction in CIA mice by suppressing osteoclastogenesis and bone resorption. Thus, our findings indicate that the targeting of PLD1 can ameliorate CIA by modulating the imbalance of Treg and Th17 cells and suppressing osteoclastogenesis, which might be a novel strategy to treat autoimmune diseases, such as RA.<\/jats:p>","DOI":"10.3390\/ijms21093230","type":"journal-article","created":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T14:00:43Z","timestamp":1588600843000},"page":"3230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Targeting of Phospholipase D1 Ameliorates Collagen-Induced Arthritis via Modulation of Treg and Th17 Cell Imbalance and Suppression of Osteoclastogenesis"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1161-5778","authenticated-orcid":false,"given":"Hyun Jung","family":"Yoo","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 46241, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9069-4576","authenticated-orcid":false,"given":"Won Chan","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 46241, Korea"},{"name":"College of Pharmacy, Yonsei University, Incheon 21983, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do Sik","family":"Min","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Yonsei University, Incheon 21983, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1016\/S0140-6736(01)06075-5","article-title":"Rheumatoid arthritis","volume":"358","author":"Lee","year":"2001","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/nri2062","article-title":"Osteoimmunology: Shared mechanisms and crosstalk between the immune and bone systems","volume":"7","author":"Takayanagi","year":"2007","journal-title":"Nat. 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