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

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.
AuthorsSarah L Jongbloed, Robert A Benson, Mohammed B Nickdel, Paul Garside, Iain B McInnes, James M Brewer
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 182 Issue 2 Pg. 963-8 (Jan 15 2009) ISSN: 1550-6606 [Electronic] United States
PMID19124739 (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
  • 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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