{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T03:02:16Z","timestamp":1770346936083,"version":"3.49.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Sialic acids are widely distributed monosaccharides in the central nervous system (CNS), where they are predominantly found as terminal sialic acid residues, as well as in di-, oligo-, and polysialic forms on the glycocalyx, collectively contributing to the development, resilience, and long-term integrity of the CNS. Harnessing sialic acid\u2013binding immunoglobulin-like lectin (Siglec) receptors by \u03b12.8-linked polysialic acids has been shown to modulate immune responses. In this study, murine and human monocytes were exposed to \u03b12.8-linked low molecular weight polysialic acid (\u03b12.8-polySIA) in vitro, followed by phenotypic, functional, and transcriptomic analyses using flow cytometry and RNA sequencing; therapeutic efficacy was assessed in mice with experimental autoimmune encephalomyelitis (EAE), a pre-clinical model of multiple sclerosis (MS). Here, we report that \u03b12.8-polySIA inhibits toll-like receptor-induced phenotypical and functional maturation of murine and human monocytes into pro-inflammatory effector cells equipped with operational antigen-presenting machinery. Moreover, RNA sequencing analyses revealed a shift towards a regulatory phenotype in human myeloid cells exposed to \u03b12.8-polySIA. Finally, therapeutic treatment with \u03b12.8-polySIA led to a milder disease course in EAE mice. Thus, by tuning myeloid cell phenotype\n                    <jats:italic>in vivo<\/jats:italic>\n                    , the therapeutic application of polysialic acid may offer a novel approach to modulate myeloid-driven inflammation in CNS autoimmunity.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1656087","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T04:14:08Z","timestamp":1760933648000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Polysialic acid restrains inflammatory monocyte 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