MiR-146a in Immunity and Disease

Abstract

MicroRNAs (miRNAs) are regulatory molecules able to influence all aspects of the biology of a cell. They have been associated with diseases such as cancer, viral infections, and autoimmune diseases, and in recent years, they also emerged as important regulators of immune responses. MiR-146a in particular is rapidly gaining importance as a modulator of differentiation and function of cells of the innate as well as adaptive immunity. Given its importance in regulating key cellular functions, it is not surprising that miR-146a expression was also found dysregulated in different types of tumors. In this paper, we summarize recent progress in understanding the role of miR-146a in innate and adaptive immune responses, as well as in disease.

Figure 1

MiR-146a negatively regulates signal transduction pathways leading to NF-κB activation. Upon activation of a cell surface receptor such as TLR4, a molecular cascade including TRAF6 and IRAK1 leads to IκBα phosphorylation and degradation and to NF-κB activation and nuclear translocation [12, 42]. NF-κB activation induces transcription of many genes, including pri-miR-146a. Once translocated to the cytoplasm and loaded onto the RISC complex, mature miR-146a contributes to attenuate receptor signaling through the downmodulation of IRAK1 and TRAF6.