Targeting TRAF1 in Psoriatic Arthritis 2989

Description Psoriatic arthritis (PsA) is an inflammatory arthritis that affects patients with psoriasis and is characterized by dysregulated immune responses and joint and skin inflammation. TRAF1 is an adaptor protein that promotes inflammatory signaling in lymphocytes and attenuates inflammatory signaling in monocytes. A weighted gene co-expression network analysis showed TRAF1 to be the central hub gene in PsA patients, however, TRAF1 levels have not been measured in PsA patients and its role in disease pathogenesis is unknown. We hypothesized that elevated TRAF1 in T cells is a key driver of PsA pathogenesis, and lowering TRAF1 levels can reduce inflammatory cytokine production and T cell activation, offering a novel therapeutic strategy for PsA disease management. Specifically, we (1) assessed TRAF1 protein expression in peripheral blood mononuclear cell (PBMC) samples by spectral flow cytometry from PsA patients (N = 55) relative to healthy donors (N = 20), and (2) examined whether knocking down TRAF1 by shRNA reduced pro-inflammatory activation and cytokine production in PsA patient PBMCs. Compared to healthy controls, PsA patients had elevated levels of TRAF1. Reduced TRAF1 levels by shRNA knockdown in PBMCs, showed a reduction in inflammatory cytokines such as, IFN?, TNF and IL-17. Our findings indicate a critical role for TRAF1 in PsA pathobiology; therefore, targeting TRAF1 in T cells may represent a promising therapeutic approach to mitigate disease activity Funding Sources Krembil Foundation Arthritis Society Canada Topic Categories Immune Mechanisms of Human Disease (HUM)