{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T18:42:39Z","timestamp":1775932959070,"version":"3.50.1"},"posted":{"date-parts":[[2025,2,20]]},"group-title":"Immunology","reference-count":62,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by recurrent inflammatory relapses and neurodegeneration. Myeloid cells play a critical role in shaping the inflammatory environment and influencing disease progression. Here, we demonstrate that activation of the Wnt signaling pathway reprograms myeloid cells into an immunoregulatory phenotype, leading to reduced neuroinflammation and disease severity. Using both experimental autoimmune encephalomyelitis (EAE) and human-derived myeloid cells, we show that Wnt agonist treatment promotes the expression of inhibitory molecules such as PD-L1 and PD-L2, suppressing pro-inflammatory responses. In the chronic and relapsing-remitting EAE models, Wnt activation significantly reduced disease severity, immune cell infiltration into the CNS, and pathogenic T cell responses. Notably, in relapsing-remitting EAE, Wnt treatment prevented new relapses in a PD-L1\u2013dependent manner, highlighting the crucial role of myeloid cell\u2013mediated immune regulation. These findings reveal a previously unrecognized role for Wnt signaling in myeloid cell immunoregulation and suggest that targeting this pathway could provide a novel therapeutic strategy for MS and other autoimmune diseases.<\/jats:p>","DOI":"10.1101\/2025.02.16.638560","type":"posted-content","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T03:21:42Z","timestamp":1740108102000},"source":"Crossref","is-referenced-by-count":0,"title":["Wnt-Activated Immunoregulatory Myeloid Cells Prevent Relapse in Experimental Autoimmune Encephalomyelitis and Offer a Potential Therapeutic Strategy for Multiple Sclerosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6144-8111","authenticated-orcid":false,"given":"Anastasia","family":"Alkhimovitch","sequence":"first","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45267"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen D.","family":"Miller","sequence":"additional","affiliation":[{"name":"Departments of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611"},{"name":"Departments of Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2945-2580","authenticated-orcid":false,"given":"Igal","family":"Ifergan","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45267"},{"name":"Department of Molecular and Cellular Biosciences, University of Cincinnati College of Medicine, Cincinnati, OH 45267"},{"name":"Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 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