MODULATION OF T CELL SIGNALING THRESHOLD AND T CELL SENSITIVITY TO ANTIGENS
摘要
MicroRNAs (miRNAs) are a diverse and abundant class of ~22-nucleotide (nt) endogenous regulatory RNAs that play a variety of roles in animal cells by controlling gene expression at the posttranscriptional level. Increased miR-181a expression in mature T cells is shown to cause a marked increase in T cell activation and augments T cell sensitivity to peptide antigens. Moreover, T cell blasts with higher miR-181a expression become reactive to antagonists. The effects of miR-181a on antigen discrimination are in part achieved by dampening the expression of multiple negative regulators in the T cell receptor (TCR) signaling pathway, including PTPN22 and the dual specificity phosphatases DUSP5 and DUSP6. This results in a reduction in the TCR signaling threshold, thus quantitatively and qualitatively enhancing T cell sensitivity to antigens.
申请公布号
WO2008057234(A2)
申请公布日期
2008.05.15
申请号
WO2007US22601
申请日期
2007.10.24
申请人
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY;LI, QI-JING;CHEN, CHANG-ZHENG;DAVIS, MARK, M.;CHAU, JACQUELINE