{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:22:00Z","timestamp":1787725320069,"version":"build-2784847793"},"posted":{"date-parts":[[2025,3,14]]},"group-title":"Immunology","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>LAMA2-deficient congenital muscular dystrophy (LAMA2-CMD) is a severe neuromuscular disorder characterized by muscle degeneration, chronic inflammation, and fibrosis. While inflammation is one the hallmarks of LAMA2-CMD, the immune cell composition in laminin-deficient muscles remains understudied. Consequently, targeted pharmacological intervention to reduce inflammation remains underexplored.<\/jats:p>\n                <jats:p>\n                  Here, we characterized the immune landscape in the dyW mouse model of LAMA2-CMD using RNA sequencing and flow cytometry. Transcriptomic analysis of dyW quadriceps femoris muscle identified 2,143 differentially expressed genes, with most upregulated genes linked to immune-related pathways.\n                  <jats:italic>Lgals3<\/jats:italic>\n                  (Galectin-3) was significantly upregulated and identified as a key upstream regulator of the immune-related pathways. Flow cytometry revealed elevated leukocyte (CD45\u207a) infiltration, with macrophages as the predominant population. Pro-inflammatory (M1) macrophages were increased, whereas anti-inflammatory (M2) macrophages remained low, indicating persistent and unresolved inflammation. Notably, Galectin-3\n                  <jats:sup>+<\/jats:sup>\n                  macrophages were significantly enriched, suggesting that Galectin-3 drives inflammation in LAMA2-CMD.\n                <\/jats:p>\n                <jats:p>\n                  Treatment of dyW mice with TD-139, a Galectin-3 inhibitor, reduced leukocyte infiltration, decreased Galectin-3\n                  <jats:sup>+<\/jats:sup>\n                  macrophages, and shifted macrophage polarization toward an M2 anti-inflammatory profile. RNA sequencing of TD-139-treated dyW muscles showed upregulation of muscle contraction pathways and downregulation of fibrosis-related genes. These findings highlight Galectin-3\n                  <jats:sup>+<\/jats:sup>\n                  macrophages as key contributors to LAMA2-CMD pathophysiology and support further exploration of TD-139 as a potential therapeutic strategy for LAMA2-CMD and other dystrophic conditions driven by chronic inflammation.\n                <\/jats:p>","DOI":"10.1101\/2025.03.12.642905","type":"posted-content","created":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T00:50:16Z","timestamp":1741999816000},"source":"Crossref","is-referenced-by-count":1,"title":["Targeting Galectin-3 to modulate inflammation in LAMA2-deficient congenital muscular dystrophy"],"prefix":"10.64898","author":[{"given":"Yonne Karoline Tenorio","family":"de Menezes","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinseo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia Qi","family":"Cheng-Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA"},{"name":"Department of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruvindi N.","family":"Ranatunga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwi U.","family":"Kemaladewi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, USA"},{"name":"Department of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041100335366000_2025.03.12.642905v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ctm.2015.05.002"},{"key":"2026041100335366000_2025.03.12.642905v1.2","first-page":"351","article-title":"Congenital muscular dystrophy with merosin deficiency","volume":"317","year":"1994","journal-title":"C R Acad Sci III"},{"key":"2026041100335366000_2025.03.12.642905v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-216"},{"key":"2026041100335366000_2025.03.12.642905v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200743"},{"key":"2026041100335366000_2025.03.12.642905v1.5","doi-asserted-by":"publisher","DOI":"10.4161\/cam.22618"},{"key":"2026041100335366000_2025.03.12.642905v1.6","doi-asserted-by":"publisher","DOI":"10.1186\/2044-5040-1-9"},{"key":"2026041100335366000_2025.03.12.642905v1.7","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410400515"},{"key":"2026041100335366000_2025.03.12.642905v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-37186-2"},{"key":"2026041100335366000_2025.03.12.642905v1.9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00735.2009"},{"key":"2026041100335366000_2025.03.12.642905v1.10","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq523"},{"key":"2026041100335366000_2025.03.12.642905v1.11","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009925"},{"key":"2026041100335366000_2025.03.12.642905v1.12","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/j.2040-4603.2018.tb00051.x","article-title":"Immunobiology of Inherited Muscular Dystrophies","volume":"8","year":"2018","journal-title":"Compr Physiol"},{"key":"2026041100335366000_2025.03.12.642905v1.13","doi-asserted-by":"publisher","DOI":"10.4103\/0972-2327.186814"},{"key":"2026041100335366000_2025.03.12.642905v1.14","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx083"},{"key":"2026041100335366000_2025.03.12.642905v1.15","doi-asserted-by":"publisher","DOI":"10.1186\/2044-5040-4-14"},{"key":"2026041100335366000_2025.03.12.642905v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.02.024"},{"key":"2026041100335366000_2025.03.12.642905v1.17","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2010.956672"},{"key":"2026041100335366000_2025.03.12.642905v1.18","doi-asserted-by":"crossref","unstructured":"Gawlik, K. 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