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Dendritic cells (DCs) can be induced to develop anti-inflammatory\/tolerogenic properties to suppress aberrant self-directed immunity by promoting immune tolerance in an antigen-specific manner. Dexamethasone can generate tolerogenic DCs and upregulates MERTK expression. As MERTK can inhibit inflammation, we investigated whether dexamethasone\u2019s tolerogenic effects are mediated via MERTK, potentially providing a novel therapeutic approach. Monocyte-derived DCs were treated with dexamethasone, and with and without MERTK ligands or MERTK inhibitors. Flow cytometry was used to assess effects of MERTK modulation on co-stimulatory molecule expression, efferocytosis, cytokine secretion and T cell proliferation. The influence on expression of Rab17, which coordinates the diversion of efferocytosed material away from cell surface presentation, was assessed. Dexamethasone-treated DCs had upregulated MERTK expression, decreased expression of co-stimulatory molecules, maturation and proliferation of co-cultured T cells and increased uptake of myelin debris. MERTK ligands did not potentiate these properties, whilst specific MERTK inhibition only reversed dexamethasone\u2019s effect on myelin uptake. Cells undergoing efferocytosis had higher Rab17 expression. Dexamethasone-enhanced efferocytosis in DCs is MERTK-dependent and could exert its tolerogenic effects by increasing Rab17 expression to prevent the presentation of efferocytosed material on the cell surface to activate adaptive immune responses.<\/jats:p>","DOI":"10.3390\/ijms242115903","type":"journal-article","created":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T09:16:21Z","timestamp":1698916581000},"page":"15903","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The Tolerogenic Influence of Dexamethasone on Dendritic Cells Is Accompanied by the Induction of Efferocytosis, Promoted by MERTK"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9889-971X","authenticated-orcid":false,"given":"Vivien","family":"Li","sequence":"first","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele D.","family":"Binder","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia"},{"name":"Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor J.","family":"Kilpatrick","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.it.2019.08.003","article-title":"Rebalancing Immune Homeostasis to Treat Autoimmune Diseases","volume":"40","author":"Horwitz","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1002\/ana.26251","article-title":"COVID-19 Vaccine Response in People with Multiple Sclerosis","volume":"91","author":"Tallantyre","year":"2022","journal-title":"Ann. 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