As an important component of innate immunity,human circulatingγδT cells function in rapid responses to infections and tumorigenesis.MicroRNAs(miRNAs)play a critical regulatory role in multiple biological processes a...As an important component of innate immunity,human circulatingγδT cells function in rapid responses to infections and tumorigenesis.MicroRNAs(miRNAs)play a critical regulatory role in multiple biological processes and diseases.Therefore,how the functions of circulating humanγδT cells are regulated by miRNAs merits investigation.In this study,we profiled the miRNA expression patterns in human peripheralγδT cells from 21 healthy donors and identified 14 miRNAs that were differentially expressed between peripheralαβT cells andγδT cells.Of the 14 identified genes,7 miRNAs were downregulated,including miR-150-5p,miR-450a-5p,miR-193b-3p,miR-365a-3p,miR-31-5p,miR-125b-5p and miR-99a-5p,whereas the other 7 miRNAs were upregulated,including miR-34a-5p,miR-16-5p,miR-15b-5p,miR-24-3p,miR-22-3p,miR-22-5p and miR-9-5p,inγδT cells compared withαβT cells.In subsequent functional studies,we found that both miR-125b-5p and miR-99a-5p downregulatedγδT cell activation and cytotoxicity to tumor cells.Overexpression of miR-125b-5p or miR-99a-5p inγδT cells inhibitedγδT cell activation and promotedγδT cell apoptosis.Additionally,miR-125b-5p knockdown facilitated the cytotoxicity ofγδT cells toward tumor cells in vitro by increasing degranulation and secretion of IFN-γand TNF-α.Our findings improve the understanding of the regulatory functions of miRNAs inγδT cell activation and cytotoxicity,which has implications for interventional approaches toγδT cell-mediated cancer therapy.展开更多
基金by the National Natural Science Foundation of China(31500725,81673010,91542117,81471574 and 31471016)CAMS Central Public Welfare Scientific Research Institute Basal Research Expenses(2016ZX310180-5 and 2017PT31004)+3 种基金the CAMS Initiative for Innovative Medicine(2016-I2M-1-008)the National Key Research and Development Program of China(2016YFA0101001 and 2016YFC0903900)Peking Union Medical College Foundation(No.3332015111)Peking Union Medical College Science Foundation for Young Scientists(No.3332015109).
文摘As an important component of innate immunity,human circulatingγδT cells function in rapid responses to infections and tumorigenesis.MicroRNAs(miRNAs)play a critical regulatory role in multiple biological processes and diseases.Therefore,how the functions of circulating humanγδT cells are regulated by miRNAs merits investigation.In this study,we profiled the miRNA expression patterns in human peripheralγδT cells from 21 healthy donors and identified 14 miRNAs that were differentially expressed between peripheralαβT cells andγδT cells.Of the 14 identified genes,7 miRNAs were downregulated,including miR-150-5p,miR-450a-5p,miR-193b-3p,miR-365a-3p,miR-31-5p,miR-125b-5p and miR-99a-5p,whereas the other 7 miRNAs were upregulated,including miR-34a-5p,miR-16-5p,miR-15b-5p,miR-24-3p,miR-22-3p,miR-22-5p and miR-9-5p,inγδT cells compared withαβT cells.In subsequent functional studies,we found that both miR-125b-5p and miR-99a-5p downregulatedγδT cell activation and cytotoxicity to tumor cells.Overexpression of miR-125b-5p or miR-99a-5p inγδT cells inhibitedγδT cell activation and promotedγδT cell apoptosis.Additionally,miR-125b-5p knockdown facilitated the cytotoxicity ofγδT cells toward tumor cells in vitro by increasing degranulation and secretion of IFN-γand TNF-α.Our findings improve the understanding of the regulatory functions of miRNAs inγδT cell activation and cytotoxicity,which has implications for interventional approaches toγδT cell-mediated cancer therapy.
