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Alnylam and Stanford University Scientists Discover New Role for,microRNAs (miRNAs) in T Cell Biology and Immunity

at Alnylam. "Moreover, this new paper in Cell continues Alnylam's commitment to scientific excellence and our broad leadership in RNAi research and its translation toward therapeutics."

T cells play a central and coordinating role in cell-mediated and acquired immunity. Recognition of both "self" and foreign molecules by T cells occurs through activation of a cell surface receptor called the T cell receptor. Activation of T cells through the T cell receptor involves the complex regulation of multiple biological pathways inside the cell. miRNAs are a broad class of small RNAs that have been shown to regulate the expression of a large number of genes in the human genome through the RNAi pathway, and many of these miRNAs are believed to be involved in disease processes. Certain miRNAs, including miR-181a, are known to play a role in B and T cell development, but their function in antigen recognition is poorly understood. Recently, Alnylam scientists and collaborators have discovered a new class of oligonucleotide therapeutics, called antagomirs, that inhibit the function of specific miRNAs in vitro and in vivo (Krutzfeldt et al. (2005) Nature 438, 685-689; Esau et al. (2006) Cell Metab., 3, 87-98).

In the current study, increasing expression of miR-181a was found to increase T cell sensitivity to antigens, while inhibiting miR-181a was found to decrease the immune response. miR-181a was found to regulate the responsiveness of the T cell receptor to antigens by the coordinated down-regulation of a set of phosphatase genes. Inhibiting miR-181a function with a selective antagomir, antagomir-181a, resulted in efficient reduction in T cell receptor sensitivity to antigens. Since abnormal T cell activity toward "self" antigens underscores the pathology in many autoimmune disorders, antagomirs selective for miR-181a could define a future therapeutic strategy for the treatment of these diseases.

About RNA Interference (RNAi)

RNA interference, or RNA
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