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

Hansson, AS; Johansson, Åsa LU and Holmdahl, Rikard LU (2004) In Arthritis Research and Therapy 6(5). p.484-491
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
relapsing polychondritis, histocompatibility complex, major, matrilin-1-induced relapsing polychondritis, IL-10, matrilin-1
in
Arthritis Research and Therapy
volume
6
issue
5
pages
484 - 491
publisher
BioMed Central
external identifiers
  • pmid:15380048
  • wos:000223992200016
  • scopus:20444373563
ISSN
1478-6362
DOI
10.1186/ar1218
language
English
LU publication?
yes
id
12425195-227d-4b02-a7cd-a8ce160b8d48 (old id 267609)
date added to LUP
2007-10-29 13:07:49
date last changed
2017-01-01 04:56:47
@article{12425195-227d-4b02-a7cd-a8ce160b8d48,
  abstract     = {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.},
  author       = {Hansson, AS and Johansson, Åsa and Holmdahl, Rikard},
  issn         = {1478-6362},
  keyword      = {relapsing polychondritis,histocompatibility complex,major,matrilin-1-induced relapsing polychondritis,IL-10,matrilin-1},
  language     = {eng},
  number       = {5},
  pages        = {484--491},
  publisher    = {BioMed Central},
  series       = {Arthritis Research and Therapy},
  title        = {Critical role of the major histocompatibility complex and IL-10 in matrilin-1-induced relapsing polychondritis in mice},
  url          = {http://dx.doi.org/10.1186/ar1218},
  volume       = {6},
  year         = {2004},
}