This pathological response primarily engages the MyD88 adaptor protein rather than the Toll/IL-1R resistance (TIR) domain–containing adapter-inducing IFN-β (TRIF)-dependent pathway, as genetic ablation of MyD88 in both A20myel-KO and A20ZF7/ZF7 mice completely prevents arthritis development, while TRIF deletion fails to mitigate disease progression (39, 41, 72). This evidence concerns the gene MYD88 and arthritic joint disease.