TLR3 and immune system disorder: Similarly, RNF31 (HOIP), one component of the LUBAC, negatively modulates TLR3 signaling induced by poly(I:C) and subsequent expression of IFNs and proinflammatory cytokines through interacting with the dsRNA-induced TLR3- signaling complex (TLR3-SC).188 The RNF31 is also required for limited TLR3-mediated cell death induced by poly(I:C) to prevent the development of immunodeficiency and autoinflammation.