Regulation of NLRP3 Inflammasome Activation by TRAF1 in Murine Models of Inflammasome-Driven Disease

The NLRP3 inflammasome is a multimeric protein complex that plays a crucial role in the activation and release of IL-1β. Unpublished in-vitro research from our lab highlights the signalling adaptor protein tumor necrosis factor receptor (TNFR) associated factor 1 (TRAF1) is an important regulator of the NLRP3 inflammasome. Understanding this regulation in-vivo is important because dysregulation of TRAF1 and the NLRP3 inflammasome is implicated in the pathogenesis of autoinflammatory diseases. To this end, two NLRP3 inflammasome-dependent in-vivo models were employed in wild-type (WT) and TRAF1 deficient (TRAF1-/-) mice. In the MSU-induced peritonitis model, TRAF1-/- mice showed increased recruitment of inflammatory leukocytes, while in the crystal-induced arthritis model, TRAF1-/- exhibited a marked increase in knee joint inflammation and expression of pro-inflammatory genes. Altogether, we demonstrate that TRAF1 plays an important role in controlling inflammasome activation and inflammasome-driven diseases, which provides insights that could lead to improved outcomes of NLRP3 inflammasome-related diseases.