The ups and downs of human UNC93B1: Autoimmune and viral conditions

Abstract

Biallelic loss-of-function UNC93B1 mutations impair TLR3 signaling in central nervous system–resident cells, underlying herpes simplex virus 1 encephalitis. Conversely, monoallelic or biallelic gain-of-function UNC93B1 mutations enhance TLR7 and/or TLR8 signaling, driving autoimmunity. Thus, in humans, UNC93B1 maintains a delicate balance between host defense and tolerance to self.