title: Innate immunity at mucosal surfaces: the IRE1-RIDD-RIG-I pathway.
abstract: Recent studies have linked the ER stress sensor IRE1α with the RIG-I pathway, which triggers an inflammatory response upon detection of viral RNAs. In response to ER dysfunction, IRE1α cleaves mRNA into single-strand fragments that lack markers of self, which activate RIG-I. Certain microbial products from mucosal pathogens activate this pathway by binding IRE1α directly, and the discovery that IRE1 is amplified at mucosal surfaces by gene duplication suggests an important role for IRE1 in mucosal immunity. Here, we review evidence in support of this hypothesis, and propose a model wherein IRE1 surveys the integrity of the ER, acting as a guard receptor and a pattern recognition receptor, capable both of sensing cellular stress caused by microbial infection and of responding to pathogens directly.
authors.affiliation: Department of Pediatrics, Harvard Medical School and Boston Children's Hospital, Boston, MA, USA; Harvard Digestive Diseases Center, Boston, MA, USA. Electronic address: Wayne.Lencer@childrens.harvard.edu.
authors.forename: Wayne I
authors.initials: WI
authors.lastname: Lencer
authors.affiliation: Department of Pediatrics, Harvard Medical School and Boston Children's Hospital, Boston, MA, USA.
authors.forename: Heidi
authors.initials: H
authors.lastname: DeLuca
authors.affiliation: Department of Pediatrics, Harvard Medical School and Boston Children's Hospital, Boston, MA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Grey
authors.affiliation: Department of Pediatrics, Harvard Medical School and Boston Children's Hospital, Boston, MA, USA; Harvard Digestive Diseases Center, Boston, MA, USA.
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Cho
mesh_terms: D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000276:immunology; D004722:Endoribonucleases / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D009092:Mucous Membrane / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000276:immunology*; D011971:Receptors, Immunologic; D013499:Surface Properties
chemical_list: D011971:Receptors, Immunologic; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
keywords: IRE1; RIG-I; inflammation; innate immunity; intestine; mucosal immunity