RIPK2 NODs to XIAP and IBD

The receptor-interacting protein kinases (RIPKs) are key regulators of inflammatory signalling and cell death pathways triggered by innate immune receptors, and RIPKs have emerged as promising therapeutic targets for treatment of immune-related disorders. RIPK2 mediates signalling responses initiated by the bacterial-sensing pattern recognition receptors nucleotide-binding oligomerization domain-containing proteins 1 and 2 (NOD1/2), which play a key role in regulation of intestinal immunity and inflammation. Modification of RIPK2 by nondegradative ubiquitin chains generated by the E3 ubiquitin ligase XIAP and other ligases govern NOD1/2 signalling. Recent advances suggest that the interaction between RIPK2 and XIAP is a druggable protein-protein interaction to modulate NOD1/2-dependent immune responses. Here, we discuss the mechanistic function of RIPK2 in immune signalling, its clinical relevance, and the on-going efforts to target RIPK2 in inflammatory bowel disease and beyond.

Automated summary

Receptor-interacting protein kinases (RIPKs) are key regulators of inflammatory signaling and cell death pathways triggered by innate immune receptors, with RIPK2 playing a crucial role in regulating intestinal immunity and inflammation. The modification of RIPK2 by nondegradative ubiquitin chains, governed by XIAP and other ligases, is essential for NOD1/2 signaling, providing a potential target for modulating immune responses. Ongoing efforts are focused on targeting RIPK2 in inflammatory bowel disease and other immune-related disorders.