Immune regulation is an essential feature of immune responses. The failure of such regulation results in allergic reactions and debilitating autoimmune diseases that can be fatal. Furthermore, the recent increase in the prevalence of the latter as well as the medical severity makes this a subject of great medical interest. Autoimmunity results from a breakdown in or the failure of the self-tolerance mechanisms. Many genes have been identified in which mutations cause the predisposition to autoinflammation and autoimmunity in human and in animal models. The relatively small number of genes explored to date unquestionably shows the challenges of identifying the associated genes in outbred populations of humans. One chief contributing gene family to both autoinflammatory and autoimmune diseases is the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family. Ever since their discovery, NLRs have drawn considerable attention for their ability to form multiprotein complexes called inflammasomes and also for their roles as NLRs, independent of inflammasome complexes. We herein first revisit general characteristics of NLRs and inflammasomes. We then couple this knowledge with the most recent findings related to autoinflammatory and autoimmune diseases, while highlighting some unanswered questions and future perspectives in elucidating NLR roles in health and disease.
Part of the book: Physiology and Pathology of Immunology