This review is provided to summarize TNFα and TNFR expression, structure, and signaling pathways, to discuss TNFR1/TNFR2 signaling in autoimmune diseases especially concerning their correlation with Tregs and organ regeneration, as well as to propose treatment strategies aimed at TNFR1/TNFR2 in autoimmune diseases. This evidence concerns the gene TNFRSF1B and autoimmune disease.