title: The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut.
abstract: Immunoglobulin A (IgA) is essential to maintain the symbiotic balance between gut bacterial communities and the host immune system. Here we provide evidence that the inhibitory co-receptor programmed cell death-1 (PD-1) regulates the gut microbiota through appropriate selection of IgA plasma cell repertoires. PD-1 deficiency generates an excess number of T follicular helper (T(FH)) cells with altered phenotypes, which results in dysregulated selection of IgA precursor cells in the germinal center of Peyer's patches. Consequently, the IgAs produced in PD-1-deficient mice have reduced bacteria-binding capacity, which causes alterations of microbial communities in the gut. Thus, PD-1 plays a critical role in regulation of antibody diversification required for the maintenance of intact mucosal barrier.
authors.affiliation: Laboratory for Mucosal Immunity, Research Center for Allergy and Immunology, RIKEN Yokohama, Tsurumi, Yokohama, Japan.
authors.forename: Shimpei
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Thinh H
authors.initials: TH
authors.lastname: Tran
authors.forename: Mikako
authors.initials: M
authors.lastname: Maruya
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Doi
authors.forename: Yumi
authors.initials: Y
authors.lastname: Tsutsui
authors.forename: Lucia M
authors.initials: LM
authors.lastname: Kato
authors.forename: Sidonia
authors.initials: S
authors.lastname: Fagarasan
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001419:Bacteria / Q000276:immunology; D058491:Bacterial Load; D018407:Bacterial Physiological Phenomena; D005243:Feces / Q000382:microbiology; D050438:Genes, Immunoglobulin Heavy Chain; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D007421:Intestine, Small / Q000276:immunology / Q000382:microbiology*; D018655:Lymphocyte Count; D051379:Mice; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology / Q000502:physiology; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000502:physiology*; D013559:Symbiosis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D007070:Immunoglobulin A; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor