title: NOD2-mediated autophagy and Crohn disease.
abstract: Autophagy is important in immune cells as a means of disposing of pathogens and in connecting with the antigen presentation machinery to facilitate immune priming and initiation of a correctly targeted adaptive immune response. While Toll-like receptors (TLRs) are known to regulate autophagy in this context, the extent to which other pattern recognition receptors (PRRs) are involved has been unclear. NOD2 is an intracellular PRR of the Nod-like receptor (NLR) family that is notable in that variants in the ligand recognition domain are associated with Crohn disease (CD). Our recent study shows NOD2 activates autophagy in a manner requiring ATG16L1, another CD susceptibility gene. NOD2 autophagy induction is required for bacterial handling and MHC class II antigen presentation in human dendritic cells (DCs). CD patients DCs expressing CD risk variant NOD2 or ATG16L1 display reduced autophagy induction after NOD2 triggering resulting in reduced bacterial killing and defective antigen presentation. Aberrant bacterial handling and immune priming could act as a trigger for inflammation in CD.
authors.affiliation: Translational Gastroenterology Unit, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Brain
authors.forename: Philip
authors.initials: P
authors.lastname: Allan
authors.forename: Alison
authors.initials: A
authors.lastname: Simmons
mesh_terms: D001343:Autophagy / Q000276:immunology*; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology* / Q000503:physiopathology; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000276:immunology*
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D053473:Nod2 Signaling Adaptor Protein