Tumor necrosis factor (TNF) is an inflammatory cytokine that, upon binding to its receptor TNFR1, can drive cytokine production, cell survival, or cell death and is a major component of an organism's anti-pathogen repetoire. It is a major guardian against infection, but when its regulation goes awry it can result in chronic inflammatory diseases that are a huge health burden. My lab tries to understand, using a combination of genetics and molecular biology, how TNF signalling is regulated with the hope that this will lead to new therapeutic opportunities. In the first part of my talk I will discuss a recently published study1 describing a new auto-inflammatory syndrome that results from loss of one level of regulation. And in the second I will discuss unpublished work that has led to the identification of a new type of post-translational modification that limits the ability of TNF to induce cell death and which may help it guard against viral infections, including coronavirus.
1Lalaoui et al, 10.1038/s41586-019-1828-5; Mutations that prevent caspase cleavage of RIPK1 cause autoinflammatory disease, Nature 2020.