{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:20:48Z","timestamp":1791566448379,"version":"4.3.4"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81701615"],"award-info":[{"award-number":["81701615"]}],"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":["81971531"],"award-info":[{"award-number":["81971531"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science and Technology Commission","doi-asserted-by":"publisher","award":["Z181100001718063"],"award-info":[{"award-number":["Z181100001718063"]}],"id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dermatomyositis (DM) associated rapidly progressive interstitial lung disease (RP-ILD) has high mortality rate and poor prognosis. Galectin-9 (Gal-9) plays multiple functions in immune regulation. We investigated Gal-9 expression in DM patients and its association with DM-ILD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 154 idiopathic inflammatory myopathy patients and 30 healthy controls were enrolled in the study. Cross-sectional and longitudinal studies were used to analyze the association between serum Gal-9 levels and clinical features. Enzyme-linked immunosorbent assay and qRT-PCR were used to examine Gal-9 expression in the sera and isolated peripheral blood mononuclear cells (PBMCs) from DM patients. Immunohistochemistry was performed to analyze the expression of Gal-9 and its ligand (T-cell immunoglobulin mucin (Tim)-3 and CD44) in lung tissues from anti-melanoma differentiation-associated gene 5 (MDA5)-positive patients. The effect of Gal-9 on human lung fibroblasts (MRC-5) was investigated\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum Gal-9 levels were significantly higher in DM patients than in immune-mediated necrotizing myopathy patients and healthy controls (all\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001). Higher serum Gal-9 levels were observed in anti-MDA5-positive DM patients than in anti-MDA5-negative DM patients [33.8 (21.9\u201344.7) vs. 16.2 (10.0\u201326.9) ng\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001]. Among the anti-MDA5-positive DM patients, serum Gal-9 levels were associated with RP-ILD severity. Serum Gal-9 levels were significantly correlated with disease activity in anti-MDA5-positive DM patients in both cross-sectional and longitudinal studies. PBMCs isolated from anti-MDA5-positive DM patients (3.7 \u00b1 2.3 ng\/mL) produced higher levels of Gal-9 than those from immune-mediated necrotizing myopathy patients (1.1 \u00b1 0.3 ng\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.022) and healthy controls (1.4 \u00b1 1.2 ng\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.045). The mRNA levels of Gal-9 were positively correlated with the levels of type-I interferon-inducible genes MX1 (\n                      <jats:italic>r<\/jats:italic>\n                      = 0.659,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.020) and IFIH1 (\n                      <jats:italic>r<\/jats:italic>\n                      = 0.787,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.002) in PBMCs from anti-MDA5-positive DM patients. Immunohistochemistry revealed increased Gal-9 and Tim-3 expression in the lung tissues of patients with DM and RP-ILD.\n                      <jats:italic>In vitro<\/jats:italic>\n                      stimulation with Gal-9 protein increased CCL2 mRNA expression in MRC-5 fibroblasts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Among anti-MDA5-positive DM patients, Gal-9 could be a promising biomarker for monitoring disease activity, particularly for RP-ILD severity. Aberrant expression of the Gal-9\/Tim-3 axis may be involved in the immunopathogenesis of DM-ILD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2021.628128","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T01:47:28Z","timestamp":1616636848000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Aberrantly Expressed Galectin-9 Is Involved in the Immunopathogenesis of Anti-MDA5-Positive Dermatomyositis-Associated Interstitial Lung Disease"],"prefix":"10.3389","volume":"9","author":[{"given":"Lin","family":"Liang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Mei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Wen","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai-Ping","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Fang","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Chun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Lin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1093\/rheumatology\/kex188","article-title":"Clinical characteristics and change in the antibody titres of patients with anti-MDA5 antibody-positive inflammatory myositis.","volume":"56","author":"Abe","year":"2017","journal-title":"Rheumatology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"5912","DOI":"10.4049\/jimmunol.169.10.5912","article-title":"Selective eosinophil adhesion to fibroblast via IFN-gamma-induced galectin-9.","volume":"169","author":"Asakura","year":"2002","journal-title":"J. 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