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

Arthritis Research & Therapy
Ann-Sofie HanssonR Holmdahl

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 (H2q) was the most susceptible, the B10.P (H2p) and B10.R (H2r) strains developed mild disease, while B10 strains carrying the v, b, f, or u H2 haplotypes were resistant. A slight variation of susceptibility of H2q strains (B10.Q> C3H.Q> DBA/1) was observed and the (B10.Q x DBA/1)F1 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 gen...Continue Reading

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Citations

Jun 10, 2005·FEBS Letters·Raimund WagenerMats Paulsson
Jan 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nathan J FelixPaul M Allen
Jul 20, 2019·Autoimmunity Reviews·Nina de MontmollinXavier Puéchal

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Methods Mentioned

BETA
transgenic
ELISA

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