{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:20:22Z","timestamp":1791148822519,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Foxp3+ T regulatory cells (Tregs) are critically important for the maintenance of immunological tolerance, immune homeostasis, and prevention of autoimmunity. Dendritic cells (DCs) are one of the major targets of Treg-mediated suppression. Some studies have suggested that Treg-mediated suppression of DC function is mediated by the interaction of CTLA-4 on Tregs with CD80\/CD86 on the DCs resulting in downregulation of CD80\/CD86 expression and a decrease in costimulation. We have re-examined the effects of Tregs on mouse DC function in a model in which Ag-specific, induced Tregs (iTregs) are cocultured with DCs in the absence of T effector cells. iTreg-treated DCs are markedly defective in their capacity to activate naive T cells. iTregs from CTLA-4\u2013deficient mice failed to induce downregulation of CD80\/CD86, but DCs treated with CTLA-4\u2013deficient iTregs still exhibited impaired capacity to activate naive T cells. The iTreg-induced defect in DC function could be completely reversed by anti\u2013IL-10, and IL-10\u2013deficient iTregs failed to downregulate DC function. iTreg-treated DCs expressed high levels of MARCH1, an E3 ubiquitin ligase, recently found to degrade CD86 and MHC class II on the DCs and expressed lower levels of CD83, a molecule involved in neutralizing the function of MARCH1. Both the enhanced expression of MARCH1 and the decreased expression of CD83 were mediated by IL-10 produced by the iTregs. Taken together, these studies demonstrate that a major suppressive mechanism of DC function by iTregs is secondary to the effects of IL-10 on MARCH1 and CD83 expression.<\/jats:p>","DOI":"10.4049\/jimmunol.1301693","type":"journal-article","created":{"date-parts":[[2013,11,11]],"date-time":"2013-11-11T23:38:25Z","timestamp":1384213105000},"page":"5875-5884","source":"Crossref","is-referenced-by-count":76,"title":["Antigen-Specific Induced T Regulatory Cells Impair Dendritic Cell Function via an IL-10\/MARCH1\u2013Dependent Mechanism"],"prefix":"10.1093","volume":"191","author":[{"given":"Gouri","family":"Chattopadhyay","sequence":"first","affiliation":[{"name":"Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan M","family":"Shevach","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,12,15]]},"reference":[{"key":"2025032406043325100_r1","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.immuni.2009.04.010","article-title":"Mechanisms of foxp3+ T regulatory cell-mediated suppression","volume":"30","author":"Shevach","year":"2009","journal-title":"Immunity"},{"key":"2025032406043325100_r2","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nri2343","article-title":"How regulatory T cells work","volume":"8","author":"Vignali","year":"2008","journal-title":"Nat. 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