microRNA regulation during the T cell development and differentiation
One of the key features of a functioning immune system is its ability to distinguish antigens of foreign origin from those derived endogenously and to mount an immune response against the former. With respect to T cells, this goal is achieved through antigen recognition by the T cell receptor (TCR) and a tightly regulated development, maintenance, and differentiation process in primary and secondary lymphoid organs. The signal transduction machinery downstream of TCR:peptide major histocompatibility complex (pMHC) engagement has been heavily studied and the detailed functions of several kinases, phosphatases, and adaptor/scaffold molecules in this pathway are well documented. Perturbation of these molecules can alter T cell activation and differentiation, thereby resulting in immune protection or tolerance. microRNAs (miRNAs) are a group of recently identified genes that produce small non-coding RNAs as final products to silence the expression of various proteins at the posttranscriptional leve. It is well appreciated that they play profound roles in development, cell lineage differentiation, virus-host interaction, and oncogenesis. Emerging evidence also indicates that they are indispensable controlling elements of the adaptive immune system. In comparison to protein-target-based immune modulation, it is straight forward to engineer an antisense-based miRNA inhibitor, and advances in chemical engineering have made in vivo delivery feasible. However, we are currently faced with an extensive knowledge gap in terms of miRNA regulation during immune cell development and function, as well as uncertainty regarding particular miRNAs’ molecular mechanisms. Our overall objective is to discover new immunoregulatory miRNAs and to employ them to modulate the strength and pattern of T cell responses for therapeutic intervention. Currently, we are devoted to dissect the function, mechanism, and upstream regulation of a group microRNAs identified under various disease condition, such as tumor, autoimmunity and chronic infection.