gli2 regulates tgf-β1 in human cd4+ t cells implications in cancer and hiv pathogenesisgli2调节tgf-β1 cd4 + t细胞的影响在人类癌症和艾滋病的发病机制.pdfVIP

GLI2 Regulates TGF-b1 in Human CD4+ T Cells: Implications in Cancer and HIV Pathogenesis Robert L. Furler1,3, Christel H. Uittenbogaart1,2,3,4* 1 Department of Microbiology, Immunology, and Molecular Genetics, David E. Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America, 2 Department of Pediatrics, David E. Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America, 3 UCLA AIDS Institute, University of California Los Angeles, Los Angeles, California, United States of America, 4 Jonsson Comprehensive Cancer Center, David E. Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America Abstract Elevated levels of the immunoregulatory cytokine TGF-b1 in cancer and HIV infection have been linked to the suppression of protective immune responses. The transcriptional regulation of TGF-b1 is complex and still not completely understood. + We report here for the first time that the transcription factor GLI2 regulates the expression of TGF-b1 in human CD4 T cells. In silico screening revealed five novel putative GLI binding sites in the human TGF-b 1 promoter. At least two of these sites within the human TGF-b 1 promoter are regulated by the GLI2 activator as knockdown of GLI2 in regulatory CD4+CD25hi T ¨ + cells, high producers of TGF-b1, significantly decreased TGF-b 1 transcription. Additionally, naıve CD4 T cells, low producers of TGF-b1, increased their basal level of TGF-b 1 mRNA following lentiviral infection with GLI2.