Overall, differences in RIPK-caspase-8 signalling requirements in arthritis pathogenesis could be due to differential cell-specific effects, levels of Cre recombinase expression, absolute levels of caspase-8 that can act as scaffolding for multiple modes of cell death [45,69,70,87,132,133], as well as environmental and genetic differences (e.g., Caspase-8lox/lox derived on a 129 [131] versus C57BL/6 [45] background). This evidence concerns the gene CASP8 and arthritic joint disease.