NLRC3 and Autoimmunity: For example, NLRC3 activation in DCs attenuates their antigen presentation function through p38 MAPK activation, which also phosphorylates USP21 (ubiquitin-specific peptidase 21, a nuclear/cytoplasmic shuttling deubiquitinase) at Ser538 to inhibit STING activity by hydrolyzing its K27/63-linked polyubiquitin chain, which limits their ability to activate CD4+T cells and their polarization to pro-inflammatory Th1 and Th17 cells to prevent against autoinflammation and autoimmunity (Figure 3) [216,217,218].