| First Author | Pan H | Year | 2013 |
| Journal | J Immunol | Volume | 191 |
| Issue | 2 | Pages | 699-707 |
| PubMed ID | 23776173 | Mgi Jnum | J:205451 |
| Mgi Id | MGI:5544882 | Doi | 10.4049/jimmunol.1201443 |
| Citation | Pan H, et al. (2013) 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. J Immunol 191(2):699-707 |
| abstractText | 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. |
