The Board of Trustees of the Leland Stanford Junior University
发明人:
Qi-Jing Li,Chang-Zheng Chen,Mark M. Davis,Jacqueline Chau
申请号:
US14288214
公开号:
US09364522B2
申请日:
2014.05.27
申请国别(地区):
US
年份:
2016
代理人:
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.