{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:04:45Z","timestamp":1790985885026,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"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":[[2013,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Dendritic cell (DC) maturation is characterized by upregulation of cell-surface MHC class II (MHC-II) and costimulatory molecules, and production of a variety of cytokines that can shape both innate and adaptive immunity. Paradoxically, transcription of the MHC-II genes, as well as its activator, CIITA, is rapidly silenced during DC maturation. The mechanisms that control CIITA\/MHC-II expression and silencing have not been fully understood. We report in this article that the tumor suppressor tuberous sclerosis complex 1 (TSC1) is a critical regulator of DC function for both innate and adaptive immunity. Its deficiency in DCs results in increased mammalian target of rapamycin (mTOR) complex 1 but decreased mTORC2 signaling, altered cytokine production, impaired CIITA\/MHC-II expression, and defective Ag presentation to CD4 T cells after TLR4 stimulation. We demonstrate further that IFN regulatory factor 4 can directly bind to CIITA promoters, and decreased IFN regulatory factor 4 expression is partially responsible for decreased CIITA\/MHC-II expression in TSC1-deficient DCs. Moreover, we identify that CIITA\/MHC-II silencing during DC maturation requires mTOR complex 1 activity. Together, our data reveal unexpected roles of TSC1\/mTOR that control multifaceted functions of DCs.<\/jats:p>","DOI":"10.4049\/jimmunol.1201443","type":"journal-article","created":{"date-parts":[[2013,6,18]],"date-time":"2013-06-18T04:50:48Z","timestamp":1371531048000},"page":"699-707","source":"Crossref","is-referenced-by-count":49,"title":["Critical Role of the Tumor Suppressor Tuberous Sclerosis Complex 1 in Dendritic Cell Activation of CD4 T Cells by Promoting MHC Class II Expression via IRF4 and CIITA"],"prefix":"10.1093","volume":"191","author":[{"given":"Hongjie","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Pediatrics-Allergy and Immunology, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Pediatrics-Allergy and Immunology, Duke University Medical Center , Durham, NC 27710"},{"name":"Department of Immunology, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Wright","sequence":"additional","affiliation":[{"name":"H. Lee Moffitt Cancer Center and Research Institute , Tampa, FL 33612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics-Allergy and Immunology, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwook","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics-Allergy and Immunology, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth L","family":"Wright","sequence":"additional","affiliation":[{"name":"H. Lee Moffitt Cancer Center and Research Institute , Tampa, FL 33612"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Ping","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics-Allergy and Immunology, Duke University Medical Center , Durham, NC 27710"},{"name":"Department of Immunology, Duke University Medical Center , Durham, NC 27710"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,7,15]]},"reference":[{"key":"2025032405084070700_r1","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0092-8674(01)00449-4","article-title":"Dendritic cells: specialized and regulated antigen processing machines","volume":"106","author":"Mellman","year":"2001","journal-title":"Cell"},{"key":"2025032405084070700_r2","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/icb.2008.14","article-title":"Monocyte-derived dendritic cells in innate and adaptive immunity","volume":"86","author":"Le\u00f3n","year":"2008","journal-title":"Immunol. 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