SFB 1054 Seminar - Li-Fan Lu
Title: MicroRNA-mediated regulation of adaptive immunity
MicroRNA (miRNA), are tightly regulated in the immune system as aberrant expression of miRNAs often results in hematopoietic malignancies and autoimmune diseases. Here, we show that the miR-23~27~24 clusters serve as cell-intrinsic molecular brakes in controlling the development and function of follicular helper T (Tfh) cells, a specific T cell subset that is essential for forming geminal centers (GCs) and promoting protective humoral immunity. Loss of the miR-23~27~24 clusters in T cells resulted in elevated frequencies of Tfh and GC B cells upon various immunological challenges whereas T cell-specific overexpression of this miRNA family led to reduced Tfh cell responses. Through targeting a network of genes that are critical for Tfh cell differentiation and function, members of the miR-23~27~24 family coordinately control Tfh cell responses and the resultant humoral immunity. On the other hand, miRNAs could also impact immune cell differentiation and function in a cell-extrinsic manner. To this end, our recent data suggest miR-155 in thymic epithelial cells (TECs) promotes thymic regulatory T (tTreg) cell development. Mechanistically, we show that mature CD80hiMHCIIhi medullary TECs (mTECs) crucial for the generation of tTreg cells express high levels of miR-155, where TEC- specific deletion of miR-155 diminishes this population. Together, through employing genetic, biochemical, and immunological approaches, we demonstrate that miRNAs play key roles in regulating both humoral and cell-mediated immune responses, two key arms in establishing protective adaptive immunity.
Host: Dietmar Zehn (B14)
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