{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:17Z","timestamp":1792790357804,"version":"4.5.0"},"posted":{"date-parts":[[2026,4,14]]},"group-title":"Immunology","reference-count":74,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"Chicago Immunoengineering Innovation Center of the University of Chicago","id":[{"id":"https:\/\/ror.org\/024mw5h28","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Alper Family Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Interleukin-10 (IL-10) is an immunoregulatory cytokine that suppresses pro-inflammatory cytokine production, myeloid cell antigen presentation, and T cell activation. However, the therapeutic use of recombinant IL-10 has been limited by its short plasma half-life and limited tissue retention, including in the secondary lymphoid organs (SLOs), key sites of autoreactive T cell priming in autoimmune disease. We previously engineered a fusion of serum albumin and IL-10 (SA-IL-10) with extended plasma half-life and enhanced accumulation in the SLOs. Here, we combine analysis of human single-cell transcriptomic data with studies in a murine experimental autoimmune encephalomyelitis (EAE) model to investigate how sustained IL-10 exposure in the SLOs modulates immune responses during neuroinflammation. Single-cell RNA-sequencing analysis of treatment-na\u00efve multiple sclerosis (MS) patients revealed a significantly elevated percentage of regulatory CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells in the cerebrospinal fluid expressing\n                  <jats:italic>IL10RA<\/jats:italic>\n                  , the ligand-binding chain of the IL-10 receptor, whereas\n                  <jats:italic>IL10<\/jats:italic>\n                  transcript detection was low and not different in MS compared to controls. Prophylactic subcutaneous administration of SA-IL-10 prevented EAE development and progression with superior efficacy to wild type IL-10 and comparable protection to fingolimod. In the SLOs, SA-IL-10 reduced antigen-specific T\n                  <jats:sub>H<\/jats:sub>\n                  17 cells, M1-like macrophages, activated dendritic cells, and antigen-induced pro-inflammatory cytokine production, while expanding M2-like macrophages and elevating the frequencies of multiple checkpoint markers on T\n                  <jats:sub>H<\/jats:sub>\n                  2 cells. SA-IL-10 also reduced immune cell infiltration in the spinal cord. Repeated SA-IL-10 administration was well tolerated in EAE, with plasma biochemistry parameters comparable to controls. Together, these findings demonstrate that increasing IL-10 exposure in the SLOs suppresses neuroinflammation by promoting immunoregulation.\n                <\/jats:p>","DOI":"10.64898\/2026.04.10.717764","type":"posted-content","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T17:35:23Z","timestamp":1776188123000},"source":"Crossref","is-referenced-by-count":0,"title":["Albumin-fused interleukin-10 prevents experimental autoimmune encephalomyelitis by promoting immunoregulation in the secondary lymphoid organs"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8510-0497","authenticated-orcid":false,"given":"Erica","family":"Budina","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, Tandon School of Engineering, New York University, Brooklyn, NY 11201, USA"},{"name":"Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL 60637, 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