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Critical role of the major histocompatibility complex and IL-10 in matrilin-1-induced relapsing polychondritis in mice

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Author

Summary, in English

Relapsing polychondritis ( RP) is an autoimmune disease that affects extra-articular cartilage. Matrilin-1-induced relapsing polychondritis (MIRP) is a model for RP and is useful for studies of the pathogenic mechanisms in this disease. There are indications that the major histocompatibility complex (MHC) class II plays a major role in RP, since DR4(+) patients are more commonly affected than controls. We have now addressed the role of the MHC region, as well as the non-MHC contribution, using congenic mouse strains. Of the MHC congenic strains, B10.Q (H2(q)) was the most susceptible, the B10.P (H2(p)) and B10.R (H2(r)) strains developed mild disease, while B10 strains carrying the v, b, f, or u H2 haplotypes were resistant. A slight variation of susceptibility of H2(q) strains (B10.Q>C3H.Q>DBA/1) was observed and the (B10.Q x DBA/1)F-1 was the most susceptible of all strains. Furthermore, macrophages and CD4(+) T cells were the most prominent cell types in inflammatory infiltrates of the tracheal cartilage. Macrophages are the major source of many cytokines, such as interleukin-10 (IL-10), which is currently being tested as a therapeutic agent in several autoimmune diseases. We therefore investigated B10.Q mice devoid of IL-10 through gene deletion and found that they developed a significantly more severe disease, with an earlier onset, than their heterozygous littermates. In conclusion, MHC genes, as well as non-MHC genes, are important for MIRP induction, and IL-10 plays a major suppressive role in cartilage inflammation of the respiratory tract.

Department/s

  • Immunology

Publishing year

2004

Language

English

Pages

484-491

Publication/Series

Arthritis Research and Therapy

Volume

6

Issue

5

Document type

Journal article

Publisher

BioMed Central (BMC)

Topic

  • Rheumatology and Autoimmunity

Keywords

  • relapsing polychondritis
  • histocompatibility complex
  • major
  • matrilin-1-induced relapsing polychondritis
  • IL-10
  • matrilin-1

Status

Published

Research group

  • Immunology

ISBN/ISSN/Other

  • ISSN: 1478-6362