title: Dendritic cell CD83 homotypic interactions regulate inflammation and promote mucosal homeostasis.
abstract: Dendritic cells (DCs) form an extensive network in the intestinal lamina propria, which orchestrates the mucosal immune response. Alterations in DC function can predispose to inflammatory bowel disease, although by unknown mechanisms. We show that CD83, a highly regulated DC cell surface protein, modulates the immune response to prevent colitis. Mice with a conditional knockout of CD83 in DCs develop exacerbated colitis following dextran sodium sulfate challenge, whereas mucosal overexpression of CD83 inhibits DC inflammatory response and protects against colitis. These CD83 perturbations can be modeled in vitro where we show that CD83 homotypic interaction occurs via cell-cell contact and inhibits pro-inflammatory responses. CD83 knockdown or cytoplasmic truncation abrogates the effects of homotypic binding. We demonstrate that CD83 homotypic interaction regulates DC activation via the mitogen-activated protein kinase pathway by inhibiting p38α phosphorylation. Our findings indicate that CD83 homotypic interactions regulate DC activation and promote mucosal homeostasis.
authors.affiliation: Department of Pathology, Genetech, South San Francisco, California, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Bates
authors.affiliation: Department of Pathology, Genetech, South San Francisco, California, USA.
authors.forename: K
authors.initials: K
authors.lastname: Flanagan
authors.affiliation: Department of Pathology, Genetech, South San Francisco, California, USA.
authors.forename: L
authors.initials: L
authors.lastname: Mo
authors.affiliation: Department of Immunology, Genetech, South San Francisco, California, USA.
authors.forename: N
authors.initials: N
authors.lastname: Ota
authors.affiliation: Department of Immunology, Genetech, South San Francisco, California, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Pathology, Genetech, South San Francisco, California, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ho
authors.affiliation: Department of Pathology, Genetech, South San Francisco, California, USA.
authors.forename: S
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Molecular Biology, Genentech, South San Francisco, California, USA.
authors.forename: M
authors.initials: M
authors.lastname: Roose-Girma
authors.affiliation: Department of Molecular Biology, Genentech, South San Francisco, California, USA.
authors.forename: S
authors.initials: S
authors.lastname: Warming
authors.affiliation: Department of Pathology, Genetech, South San Francisco, California, USA.
authors.forename: L
authors.initials: L
authors.lastname: Diehl
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication; D003092:Colitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006706:Homeostasis; D018928:Immunity, Mucosal; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D016130:Immunophenotyping; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D015398:Signal Transduction; D000097802:CD83 Antigen
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen