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The protective effect was mediated through the induction of tolerogenic CD11C+CD8\u03b1\u2212 dendritic cells (DCs) and consequent expansion of Foxp3+ regulatory T cells (Tregs). Subsequently, we showed that GM-CSF acted specifically on bone marrow precursors and facilitated their differentiation into tolerogenic dendritic cells (DCs; GM-CSF\u2013induced bone marrow-derived DCs [GM-BMDCs]), which directed Treg expansion in a contact-dependent manner. This novel mechanism of Treg expansion was independent of TCR-mediated signaling but required exogenous IL-2 and cosignaling from DC-bound OX40L. In this study, we observed that OX40L-mediated signaling by GM-BMDCs, although necessary, was not sufficient for Treg expansion and required signaling by Jagged1. Concurrent signaling induced by OX40L and Jagged1 via OX40 and Notch3 receptors expressed on Tregs was essential for the Treg expansion with sustained FoxP3 expression. Adoptive transfer of only OX40L+Jagged1+ BMDCs led to Treg expansion, increased production of IL-4 and IL-10, and suppression of EAT in the recipient mice. These results showed a critical role for OX40L- and Jagged1-induced cosignaling in GM-BMDC\u2013induced Treg expansion.<\/jats:p>","DOI":"10.4049\/jimmunol.1202298","type":"journal-article","created":{"date-parts":[[2013,4,30]],"date-time":"2013-04-30T03:01:52Z","timestamp":1367290912000},"page":"5516-5525","source":"Crossref","is-referenced-by-count":61,"title":["OX40L\/Jagged1 Cosignaling by GM-CSF\u2013Induced Bone Marrow-Derived Dendritic Cells Is Required for the Expansion of Functional Regulatory T Cells"],"prefix":"10.1093","volume":"190","author":[{"given":"Anupama","family":"Gopisetty","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Illinois at Chicago , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palash","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Illinois at Chicago , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Haddad","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Illinois at Chicago , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Joseph C","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Illinois at Chicago , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenthamarakshan","family":"Vasu","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hollings Cancer Center, College of Medicine, Medical University of South Carolina , Charleston, SC 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Miele","sequence":"additional","affiliation":[{"name":"Department of Medicine, The University of Mississippi Medical Center , Jackson, MS 39216"},{"name":"Department of Pharmacology, The University of Mississippi Medical Center , Jackson, MS 39216"},{"name":"Department of Biochemistry, The University of Mississippi Medical Center , Jackson, MS 39216"},{"name":"Department of Radiation Oncology, The University of Mississippi Medical Center , Jackson, MS 39216"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bellur S","family":"Prabhakar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Illinois at Chicago , Chicago, IL 60612"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,6,1]]},"reference":[{"key":"2025032407040723600_r1","doi-asserted-by":"crossref","first-page":"5511","DOI":"10.4049\/jimmunol.170.11.5511","article-title":"Selective induction of dendritic cells using granulocyte macrophage-colony stimulating factor, but not fms-like tyrosine kinase receptor 3-ligand, activates thyroglobulin-specific CD4+\/CD25+ T cells and suppresses experimental autoimmune thyroiditis","volume":"170","author":"Vasu","year":"2003","journal-title":"J. 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