{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:56:51Z","timestamp":1787169411997,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012537","name":"Ditmanson Medical Foundation Chia-Yi Christian Hospital","doi-asserted-by":"publisher","award":["R111-045"],"award-info":[{"award-number":["R111-045"]}],"id":[{"id":"10.13039\/501100012537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012537","name":"Ditmanson Medical Foundation Chia-Yi Christian Hospital","doi-asserted-by":"publisher","award":["MOST 106-2320-B-006-074"],"award-info":[{"award-number":["MOST 106-2320-B-006-074"]}],"id":[{"id":"10.13039\/501100012537","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Science and Technology Council","award":["R111-045"],"award-info":[{"award-number":["R111-045"]}]},{"name":"National Science and Technology Council","award":["MOST 106-2320-B-006-074"],"award-info":[{"award-number":["MOST 106-2320-B-006-074"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with enhanced NETosis and impaired degradation of neutrophil extracellular traps (NETs). Galectin-3 is a \u03b2-galactoside binding protein and is associated with neutrophil functions as well as involved in mediating autoimmune disorders. In this study, we plan to examine the associations of galectin-3 with the pathogenesis of SLE and NETosis. Galectin-3 expression levels were determined in peripheral blood mononuclear cells (PBMCs) of SLE patients for the association with lupus nephritis (LN) or correlation of SLE disease activity index 2000 (SLEDAI-2K). NETosis was observed in human normal and SLE and murine galectin-3 knockout (Gal-3 KO) neutrophils. Gal-3 KO and wild-type (WT) mice induced by pristane were used to evaluate disease signs, including diffuse alveolar haemorrhage (DAH), LN, proteinuria, anti-ribonucleoprotein (RNP) antibody, citrullinated histone 3 (CitH3) levels, and NETosis. Galectin-3 levels are higher in PBMCs of SLE patients compared with normal donors and positively correlated with LN or SLEDAI-2K. Gal-3 KO mice have higher percent survival and lower DAH, LN proteinuria, and anti-RNP antibody levels than WT mice induced by pristane. NETosis and citH3 levels are reduced in Gal-3 KO neutrophils. Furthermore, galectin-3 resides in NETs while human neutrophils undergo NETosis. Galectin-3-associated immune complex deposition can be observed in NETs from spontaneously NETotic cells of SLE patients. In this study, we provide clinical relevance of galectin-3 to the lupus phenotypes and the underlying mechanisms of galectin-3-mediated NETosis for developing novel therapeutic strategies targeting galectin-3 for SLE.<\/jats:p>","DOI":"10.3390\/ijms24119493","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T04:40:51Z","timestamp":1685508051000},"page":"9493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Galectin-3 Mediates NETosis and Acts as an Autoantigen in Systemic Lupus Erythematosus-Associated Diffuse Alveolar Haemorrhage"],"prefix":"10.3390","volume":"24","author":[{"given":"Shih-Yao","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Nursing, College of Nursing, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Teng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan"},{"name":"Department of Internal Medicine, School of Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin-Yu","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrong-Reen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan"},{"name":"Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2449-8547","authenticated-orcid":false,"given":"Ai-Li","family":"Shiau","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan"},{"name":"Ditmanson Medical Foundation Chia-Yi Christian Hospital, Zhongxiao Road 539, East District, Chiayi 60002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Hsi","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7821-9406","authenticated-orcid":false,"given":"Chao-Liang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"},{"name":"Ditmanson Medical Foundation Chia-Yi Christian Hospital, Zhongxiao Road 539, East District, Chiayi 60002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1038\/nrrheum.2016.186","article-title":"New insights into the immunopathogenesis of systemic lupus erythematosus","volume":"12","author":"Tsokos","year":"2016","journal-title":"Nat. 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