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This review explores the phenotypic and functional heterogeneity of DCs and their specialized roles in regulating the immune response, with a focus on pathways that confer tolerogenic properties to DCs. Furthermore, we discuss emerging strategies for the therapeutic induction of a tolerogenic phenotype in DCs in the setting of autoimmune diseases. A better understanding of the molecular mechanisms that control the tolerogenic phenotype of DCs may open new avenues for the development of efficacious and safe immunotherapies for autoimmune, allergic, and chronic inflammatory diseases.<\/jats:p>","DOI":"10.1111\/imr.70073","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:16:02Z","timestamp":1763025362000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Dendritic Cells: Orchestrators of Immune Responsiveness and Tolerance"],"prefix":"10.1111","volume":"336","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-0161","authenticated-orcid":false,"given":"Carolina M.","family":"Polonio","sequence":"first","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts 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