Contrasting contributions of TNF from distinct cellular sources in arthritis

Anti-tumour necrosis factor (TNF) therapy is widely used as a treatment for rheumatoid arthritis (RA). However, Andrey Kruglov and Sergei Nedospasov from DRFZ have found deleterious and protective TNF functions in arthritis to distinct cellular sources and molecular forms. TNF produced by myeloid cells controls arthritis induction through regulation of synovial fibroblast activation, while B cell-derived TNF regulates severity via induction of autoantibodies. Instead, TNF produced by T cells limits arthritis development via control of T cell responses during induction phase of arthritis but is dispensable for the pathogenesis. Thus a cell type-specific TNF blockade for patients with RA may be superior to pan-anti-TNF therapy.