{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:43:41Z","timestamp":1785908621726,"version":"3.56.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by immune-mediated demyelination and neuroinflammation resulting from the breakdown of self-tolerance. Tolerogenic dendritic cells (tolDC) have emerged as a promising therapeutic strategy to restore antigen-specific immune tolerance; however, generating stable tolDC under inflammatory conditions remains challenging. Although interferon (IFN)-\u03b3 is traditionally regarded as a pro-inflammatory cytokine, accumulating evidence indicates that it can also exert protective and immunoregulatory functions in specific cellular and disease contexts. Here, we investigated whether low-dose IFN-\u03b3 directly programs dendritic cells (DC) toward a stable tolerogenic phenotype with therapeutic relevance for MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Murine bone marrow-derived DC were differentiated in the presence of IFN-\u03b3 and evaluated for phenotype, cytokine production, and T-cell modulatory capacity. Therapeutic efficacy was assessed in experimental autoimmune encephalomyelitis (EAE). Translational relevance was examined using monocyte-derived DC from treatment-na\u00efve MS patients and healthy donors (HD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      IFN-\u03b3-conditioned DC displayed reduced expression of co-stimulatory molecules and MHC-II, increased PD-L1 expression, and diminished pro-inflammatory cytokine production. Functionally, these cells suppressed myelin antigen-driven CD4\n                      <jats:sup>+<\/jats:sup>\n                      T-cell proliferation and activation while promoting FoxP3\n                      <jats:sup>+<\/jats:sup>\n                      regulatory T-cell differentiation. Adoptive transfer of myelin-derived peptide-loaded IFN-\u03b3-conditioned DC significantly ameliorated established EAE and induced sustained clinical improvement, even after inflammatory challenge, demonstrating phenotypic and functional stability. In human studies, IFN-\u03b3 induced comparable tolerogenic phenotypes in DC from MS patients and HD; however, only MS-derived IFN-\u03b3-conditioned DC effectively suppressed CD4\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell responses. Residual CD80 expression correlated with T1 lesion burden.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, these findings uncover a previously underappreciated context-dependent immunoregulatory role of IFN-\u03b3 in DC biology and immune tolerance. Furthermore, IFN-\u03b3-induced DC emerge as a promising therapeutic strategy to restore immune tolerance in MS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1893121","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:43:47Z","timestamp":1785905027000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Interferon-\u03b3-induced tolerogenic dendritic cells ameliorate autoimmune neuroinflammation and suppress T-cell responses in multiple sclerosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Constanza","family":"Vilchez","sequence":"first","affiliation":[{"name":"Interdisciplinary Nucleus of Pharmacology and Immunology, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Parra-Tello","sequence":"additional","affiliation":[{"name":"Interdisciplinary Nucleus of Pharmacology and Immunology, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis F.","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Interdisciplinary Nucleus of Pharmacology and Immunology, Instituto de Ciencias Biom\u00e9dicas (ICBM), Facultad de Medicina, Universidad de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Noriega","sequence":"additional","affiliation":[{"name":"Oficina de Apoyo a la Investigaci\u00f3n Cl\u00ednica (OAIC), Facultad de Medicina, Hospital Cl\u00ednico Universidad de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Carri\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Research and Innovation, Faculty of Health Sciences, Universidad del Alba","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad San Sebasti\u00e1n","place":["Santiago, Chile"]},{"name":"Laboratorio de Neuroinmunolog\u00eda, Centro Cient\u00edfico y Tecnol\u00f3gico de Excelencia Ciencia & Vida, Fundaci\u00f3n Ciencia & Vida","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Prado","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad San Sebasti\u00e1n","place":["Santiago, Chile"]},{"name":"Laboratorio de Neuroinmunolog\u00eda, Centro Cient\u00edfico y Tecnol\u00f3gico de Excelencia 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