The spectrum of NLR and related molecules in human disease.

The nucleotide-binding and oligomerisation domain, leucine rich repeat (NOD-like receptors or NLRs) family of intracellular pathogen recognition receptors (PRRs) is involved in the pathogenesis of a number of rare and more common monogenic diseases, and is increasingly being recognised to play a pivotal role in polygenic complex diseases. The recognition of bacterial wall constituents and other cellular stressor molecules by different NLRs leads to activation of the innate immune response and upregulation of key proinflammatory pathways, such as IL-1β and IL-18 cytokine production and translocation of NF-κB transcription factor to the nucleus. These signalling pathways are increasingly being targeted as potential sites for new therapies. This presentation will discuss the role of NLRs in monogenic autoinflammatory disease and also in complex diseases, where IL-1β and IL-18 cytokines underlie the pathogenesis. It will also describe the success to date of therapeutic agents in treating some of the disorders associated with aberrant NLR function.