Fig. 3.

ADAR1-mediated MDA5 tolerance to self-dsRNAs in innate and adaptive immune cells. Melanoma differentiation-associated protein 5 (MDA5) senses viral RNAs upon infection, promoting polymerization of mitochondrial anti-viral-signaling protein (MAVS), and leading to the expression of interferon-stimulated genes (ISGs). To avoid the recognition of self-double-stranded (ds)RNAs by MDA5, adenosine deaminase acting on RNA 1 (ADAR1)-mediated RNA editing is required. Loss of ADAR1 results in activation of the MDA5–MAVS signaling pathway, which impairs homeostasis of innate immune cells, such as dendritic cells (DCs) and macrophages, as well as adaptive immune cells, such as T and B cells