title: Plasmacytoid dendritic cells regulate breach of self-tolerance in autoimmune arthritis.
abstract: Achieving remission in rheumatoid arthritis (RA) remains elusive despite current biological therapeutics. Consequently, interest has increased in strategies to re-establish immune tolerance to provide long-term disease suppression. Although dendritic cells (DC) are prime candidates in initiating autoreactive T cell responses, and their presence within the synovial environment suggests a role in generation and maintenance of autoreactive, synovial T cell responses, their functional importance remains unclear. We investigated the contribution made by plasmacytoid DCs (pDCs) in the spontaneous breach of tolerance to arthritis-related self proteins, including rheumatoid factor, citrullinated peptide, and type II collagen observed in a novel arthritis model. Selective pDC depletion in vivo enhanced the severity of articular pathology and enhanced T and B cell autoimmune responses against type II collagen. pDC may offer a net anti-inflammatory function in the context of articular breach of tolerance. Such data will be vital in informing DC modulatory/therapeutic approaches.
authors.affiliation: Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, Glasgow, UK.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Jongbloed
authors.forename: Robert A
authors.initials: RA
authors.lastname: Benson
authors.forename: Mohammed B
authors.initials: MB
authors.lastname: Nickdel
authors.forename: Paul
authors.initials: P
authors.lastname: Garside
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: James M
authors.initials: JM
authors.lastname: Brewer
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010456:Peptides, Cyclic / Q000276:immunology; D012217:Rheumatoid Factor / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000637:transplantation
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D024043:Collagen Type II; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D010047:Ovalbumin; D005620:Freund's Adjuvant; D012217:Rheumatoid Factor