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Plasmacytoid dendritic cells regulate breach of self-tolerance in autoimmune arthritis

Jongbloed, S.L. and Benson, R.A. and Nickdel, M.B. and Garside, P. and McInnes, L.B. and Brewer, J.M. (2009) Plasmacytoid dendritic cells regulate breach of self-tolerance in autoimmune arthritis. Journal of Immunology, 182 (2). pp. 963-968. ISSN 0022-1767

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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.