发明名称 |
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 sensitDynaivity to antigens. |
申请公布号 |
US9598695(B2) |
申请公布日期 |
2017.03.21 |
申请号 |
US201615165762 |
申请日期 |
2016.05.26 |
申请人 |
The Board of Trustees of the Leland Stanford Junior University |
发明人 |
Li Qi-Jing;Chen Chang-Zheng;Davis Mark M.;Chau Jacqueline |
分类号 |
A61K48/00;C07H21/02;C07H21/04;C12N15/113;G01N33/50;A61K39/00 |
主分类号 |
A61K48/00 |
代理机构 |
Bozicevic, Field & Francis LLP |
代理人 |
Sherwood Pamela J.;Bozicevic, Field & Francis LLP |
主权项 |
1. A method of decreasing T cell activity to an autoantigen, the method comprising:
reducing the activity of miR-181a in peripheral T cells of an individual with a T cell mediated autoimmune disease by administering a modified oligonucleotide that is complementary to miR-181a, wherein the oligonucleotide is at least 12 but not more than 25 nucleotides in length and has no more than 2 mismatches over its length compared to an equal length portion of miR-181a; and thereby raising T cell receptor signaling threshold and decreasing T cell sensitivity to antigen. |
地址 |
Standford CA US |