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	Sarah L Jongbloed, Robert A Benson, Mohammed B Nickdel, Paul Garside, Iain B McInnes, James M Brewer
Journal	Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 182 Issue 2 Pg. 963-8 (Jan 15 2009) ISSN: 1550-6606 [Electronic] United States
PMID	19124739 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Autoantibodies Autoantigens Collagen Type II Peptides, Cyclic cyclic citrullinated peptide Ovalbumin Freund's Adjuvant Rheumatoid Factor
Topics	Adoptive Transfer Animals Arthritis, Experimental (immunology, metabolism, pathology) Autoantibodies (biosynthesis, blood) Autoantigens (immunology) Autoimmune Diseases (immunology, metabolism, pathology) Cells, Cultured Collagen Type II (immunology) Dendritic Cells (immunology, pathology) Female Freund's Adjuvant (administration & dosage) Mice Mice, Inbred BALB C Mice, Transgenic Ovalbumin (administration & dosage, immunology) Peptides, Cyclic (immunology) Rheumatoid Factor (immunology) Self Tolerance (immunology) Th1 Cells (immunology, transplantation)

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