{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T07:48:02Z","timestamp":1781941682219,"version":"3.54.5"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology Taiwan, Republic of China","award":["110-2314-B-016-060"],"award-info":[{"award-number":["110-2314-B-016-060"]}]},{"name":"Ministry of Science and Technology Taiwan, Republic of China","award":["111-2314-B-016-025"],"award-info":[{"award-number":["111-2314-B-016-025"]}]},{"name":"Ministry of Science and Technology Taiwan, Republic of China","award":["MND-MAB-110-133"],"award-info":[{"award-number":["MND-MAB-110-133"]}]},{"name":"Ministry of National Defense Medical Affairs Bureau","award":["110-2314-B-016-060"],"award-info":[{"award-number":["110-2314-B-016-060"]}]},{"name":"Ministry of National Defense Medical Affairs Bureau","award":["111-2314-B-016-025"],"award-info":[{"award-number":["111-2314-B-016-025"]}]},{"name":"Ministry of National Defense Medical Affairs Bureau","award":["MND-MAB-110-133"],"award-info":[{"award-number":["MND-MAB-110-133"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is an autoimmune disease with chronic inflammation, bone erosion, and joint deformation. Synovial tissue in RA patients is full of proinflammatory cytokines and infiltrated immune cells, such as T help (Th) 9, Th17, macrophages, and osteoclasts. Recent reports emphasized a new member of the interleukin (IL)-10 family, IL-26, an inducer of IL-17A that is overexpressed in RA patients. Our previous works found that IL-26 inhibits osteoclastogenesis and conducts monocyte differentiation toward M1 macrophages. In this study, we aimed to clarify the effect of IL-26 on macrophages linking to Th9 and Th17 in IL-9 and IL-17 expression and downstream signal transduction. Murine and human macrophage cell lines and primary culture cells were used and stimulated by IL26. Cytokines expressions were evaluated by flow cytometry. Signal transduction and transcription factors expression were detected by Western blot and real time-PCR. Our results show that IL-26 and IL-9 colocalized in macrophage in RA synovium. IL-26 directly induces macrophage inflammatory cytokines IL-9 and IL-17A expression. IL-26 increases the IL-9 and IL-17A upstream mechanisms IRF4 and RelB expression. Moreover, the AKT-FoxO1 pathway is also activated by IL-26 in IL-9 and IL-17A expressing macrophage. Blockage of AKT phosphorylation enhances IL-26 stimulating IL-9-producing macrophage cells. In conclusion, our results support that IL-26 promotes IL-9- and IL-17-expressing macrophage and might initiate IL-9- and IL-17-related adaptive immunity in rheumatoid arthritis. Targeting IL-26 may a potential therapeutic strategy for rheumatoid arthritis or other IL-9 plus IL-17 dominant diseases.<\/jats:p>","DOI":"10.3390\/ijms24087526","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T03:25:11Z","timestamp":1681961111000},"page":"7526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Interleukin 26 Induces Macrophage IL-9 Expression in Rheumatoid Arthritis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0346-9093","authenticated-orcid":false,"given":"Yi-Hsun","family":"Wang","sequence":"first","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4630-2103","authenticated-orcid":false,"given":"Yi-Jen","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Cheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Rheumatology\/Immunology and Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4302-8196","authenticated-orcid":false,"given":"Gu-Jiun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department and Graduate Institute of Biology and Anatomy, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shing-Hwa","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Breast Surgery, Department of Surgery, New Taipei City Hospital, New Taipei City 241204, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huey-Kang","family":"Sytwu","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 35053, Taiwan"},{"name":"Department of Microbiology and Immunology, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Pi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan"},{"name":"Department and Graduate Institute of Biology and Anatomy, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1093\/rheumatology\/39.2.122","article-title":"The links between joint damage and disability in rheumatoid arthritis","volume":"39","author":"Scott","year":"2000","journal-title":"Rheumatol. 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