The molecular mechanism of autoinflammatory disease: Lessons from the function of NOD protein families

Abstract

The latest decade, our understanding of pattern-recognizing receptors involved in innate immune system has been accumulated. One class of the pattern recognizing receptors, the toll-like receptors (TLRs) are well known to detect extracellular pathogens on the cell surface membrane. On the other hand, recently discovered the nucleotide-binding oligomerization domain proteins (NoDs) are involved in recognizing intracellular pathog ens. Since Nod2, one of the NODs, mutations were found to associate with susceptibility of Crohn's disease, the NODs have been highlighted. For example, cryopyrin mutations have been reported to associate with Familial cold urticaria (FCU)/Familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), Neonatal onset multisystem inflammatory disease (NOMID)/Chronic infantile neurologic cutaneous and articular syndrome (CINCA). Here, we summarize the discovery of the NODs and related molecules, and also discuss the function of the NODs and molecular mechanisms of the autoinlammatory diseases. © 2007, The Japan Society for Clinical Immunology. All rights reserved.