TNF and autoimmune disease: In summary, germline mutations in genes regulating the granule-mediated cytotoxicity, innate immune system, and inflammasome activation were the leading causes of autoinflammatory diseases and autoimmune diseases triggering CRS, while CD8 T cells and innate cells are most likely the primary driver cells, which produce and release TNF, IFN-γ, IL-1, and a combination of other cytokines to drive pathogenesis of these diseases.1