title: Regulation of MHC class I expression by Foxp3 and its effect on regulatory T cell function.
abstract: Expression of MHC class I molecules, which provide immune surveillance against intracellular pathogens, is higher on lymphoid cells than on any other cell types. In T cells, this is a result of activation of class I transcription by the T cell enhanceosome consisting of Runx1, CBFβ, and LEF1. We now report that MHC class I transcription in T cells also is enhanced by Foxp3, resulting in higher levels of class I in CD4(+)CD25(+) T regulatory cells than in conventional CD4(+)CD25(-) T cells. Interestingly, the effect of Foxp3 regulation of MHC class I transcription is cell type specific: Foxp3 increases MHC class I expression in T cells but represses it in epithelial tumor cells. In both cell types, Foxp3 targets the upstream IFN response element and downstream core promoter of the class I gene. Importantly, expression of MHC class I contributes to the function of CD4(+)CD25(+) T regulatory cells by enhancing immune suppression, both in in vitro and in vivo. These findings identify MHC class I genes as direct targets of Foxp3 whose expression augments regulatory T cell function.
authors: Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors: Jie
authors: J
authors: Mu
authors: Xuguang
authors: X
authors: Tai
authors: Shankar S
authors: SS
authors: Iyer
authors: Jocelyn D
authors: JD
authors: Weissman
authors: Alfred
authors: A
authors: Singer
authors: Dinah S
authors: DS
authors: Singer
mesh_terms: D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics / Q000276:immunology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin