Abstract
Fast immune responses are mediated by innate immune receptors that react against conserved structures in pathogens, named pathogen-associated molecular patterns（PAMPs）and endogenous danger-associated molecular patterns （DAMPS）. PAMPS include lipopolysaccharides, peptidoglycan, and endogenous DAMPS include uric acid and cholesterol deposits. Innate immune system consist of two groups, toll-like receptors （TLRs）and nucleotide binding oligomerization domain（NOD）-like receptors（NLR）. NLRs recognize pathogens in the cytosol. We have previously revealed that multiple genetic variants of NOD1 and NOD2, components of NLRs, are associated with susceptibility to several diseases. Notably, NOD2 loss-of-function and gain-of-function mutations showed susceptibility to Crohn’s disease and Blau syndrome（early-onset sarcoidosis：EOS）, respectively. Furthermore, we have revealed that impaired recognition of intracellular Propionibacterium acnes resulting from a polymorphism in the NOD1 gene is involved in the increased susceptibility of Sarcoidosis in a Japanese population. Inflammasome, newly identified innate immune system, activates IL-1β and causes several lifestyle diseases including diabetes mellitus and atherosclerosis. Manipulating the activities of innate immune factors may produce new therapy for lifestyle diseases.
