title: Gut microbiota as a source of a surrogate antigen that triggers autoimmunity in an immune privileged site.
abstract: Recent discoveries on the role of commensal microbiota have significantly changed our understanding of human physiology. The host-microbiota interplay is now an important aspect to take into account to understand immune responses and immunological diseases. Autoimmune uveitis is a sight-threatening disease that arises without a known infectious etiology. It is unknown where and how autoreactive T cells become primed to trigger disease in the eye, which is an immune privileged site. We recently reported data supporting the notion that retina-specific T cells receive a signal in the gut from commensal microbiota-derived cross-reactive antigen(s) and trigger autoimmune uveitis in the R161H mouse model. Here we discuss our published findings, as well as our recent attempts to identify the responsible microbe(s) by using different antibiotic treatments, 16S rDNA sequencing and homology searches for candidate antigenic mimic(s) of the retinal antigen.
authors.affiliation: a Laboratory of Immunology , National Eye Institute, National Institutes of Health , Bethesda , Maryland , USA.|b Laboratory of Immunoregulation, Department of Microbiology , Immunology and Parasitology, Federal University of Santa Catarina , Florianopolis , Brazil.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Zárate-Bladés
authors.affiliation: a Laboratory of Immunology , National Eye Institute, National Institutes of Health , Bethesda , Maryland , USA.
authors.forename: Reiko
authors.initials: R
authors.lastname: Horai
authors.affiliation: a Laboratory of Immunology , National Eye Institute, National Institutes of Health , Bethesda , Maryland , USA.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Mattapallil
authors.affiliation: c Alkek Center for Metagenomics and Microbiome Research and Department of Molecular Virology and Microbiology , Baylor College of Medicine , Houston , Texas , USA.
authors.forename: Nadim J
authors.initials: NJ
authors.lastname: Ajami
authors.affiliation: c Alkek Center for Metagenomics and Microbiome Research and Department of Molecular Virology and Microbiology , Baylor College of Medicine , Houston , Texas , USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Wong
authors.affiliation: c Alkek Center for Metagenomics and Microbiome Research and Department of Molecular Virology and Microbiology , Baylor College of Medicine , Houston , Texas , USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Petrosino
authors.affiliation: d Bio-Technical Center, Japan SLC, Inc. , Hamamatsu , Shizuoka , Japan.
authors.forename: Kikuji
authors.initials: K
authors.lastname: Itoh
authors.affiliation: a Laboratory of Immunology , National Eye Institute, National Institutes of Health , Bethesda , Maryland , USA.
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.affiliation: a Laboratory of Immunology , National Eye Institute, National Institutes of Health , Bethesda , Maryland , USA.
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Caspi
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000382:microbiology*; D015551:Autoimmunity; D000069196:Gastrointestinal Microbiome; D006801:Humans; D012160:Retina / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014605:Uveitis / Q000276:immunology* / Q000382:microbiology*
chemical_list: D000941:Antigens
keywords: T cell; autoimmune uveitis; immune privilege; interphotoreceptor retinoid-binding protein (IRBP); microbiota; retina