title: Interplay of autophagy and innate immunity in Crohn's disease: a key immunobiologic feature.
abstract: Crohn's disease representing a clinical phenotype of inflammatory bowel disease is a polygenic immune disorder with complex multifactor etiology. Recent genome-wide association studies of susceptibility loci have highlighted on the importance of the autophagy pathway, which previously had not been implicated in disease pathology. Autophagy represents an evolutionarily highly conserved multi-step process of cellular self-digestion due to sequestration of excessive, damaged, or aged proteins and intracellular organelles in double-membranous vesicles of autophagosomes, terminally self-digested in lysosomes. Autophagy is deeply involved in regulation of cell development and differentiation, survival and senescence, and it also fundamentally affects the inflammatory pathways, as well as the innate and adaptive arms of immune responses. Autophagy is mainly activated due to sensors of the innate immunity, i.e., by pattern recognition receptor signaling. The interplay of genes regulating immune functions is strongly influenced by the environment, especially gut resident microbiota. The basic challenge for intestinal immune recognition is the requirement of a simultaneous delicate balance between tolerance and responsiveness towards microbes. On the basis of autophagy-related risk genetic polymorphisms (ATG16L1, IRGM, NOD2, XBP1) impaired sensing and handling of intracellular bacteria by innate immunity, closely interrelated with the autophagic and unfolded protein pathways seem to be the most relevant immunobiologic events. Autophagy is now widely considered as a key regulator mechanism with the capacity to integrate several aspects of Crohn's disease pathogenesis. In this review, recent advances in the exciting crosstalk of susceptibility coding variants-related autophagy and innate immunity are discussed.
authors.affiliation: 2nd Department of Internal Medicine, Semmelweis University, 1088 Budapest, Hungary. muzes.gyorgyi@med.semmelweis-univ.hu
authors.forename: Györgyi
authors.initials: G
authors.lastname: Műzes
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sipos
mesh_terms: D001343:Autophagy; D001419:Bacteria / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007422:Intestines / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011971:Receptors, Immunologic
keywords: Autophagy; Autophagy genes; Crohn's disease; Gut microbiota; Innate immunity
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