The point mutation of tyrosine 759 of the IL-6 family cytokine receptor gp130 synergizes with HTLV-1 pX in promoting rheumatoid arthritis-like arthritis

Katsuhiko Ishihara, Shin Ichiro Sawa, Hideto Ikushima, Seiichi Hirota, Toru Atsumi, Daisuke Kamimura, Sung Joo Park, Masaaki Murakami, Yukihiko Kitamura, Yoichiro Iwakura, Toshio Hirano

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Abstract

Rheumatoid arthritis (RA) is a polygenic autoimmune disease. The autoimmunity develops from synergistic actions of genetic and environmental factors. We generated a double-mutant mouse by crossing two murine models of RA, a gp130 mutant knock-in mouse (gp130F759/F759) and an HTLV-1 pX transgenic mouse (pX-Tg), in a C57BL/6 background, which is resistant to arthritis. The mice spontaneously developed severe arthritis with a much earlier onset than the gp130F759/F759 mice and with a much higher incidence than did the pX-Tg mice. The symptoms of gp130F759/F759 mice, including lymphoadenopathy, splenomegaly, hyper-γ-globulinemia, autoantibody production, increases in memory/activated T cells and granulocytes in the peripheral lymphoid organs, and a decrease in the class II MHCbright CD11c+ population, were augmented in the double mutants. Marked reductions in incidence, severity and immunological abnormalities were seen in the triple mutant, IL-6-/-/gp130F759/F759/pX-Tg, indicating that the arthritis in the double mutant is IL-6 dependent. gp130F759/F759/pX-Tg is a unique mouse model for RA.

Original languageEnglish
Pages (from-to)455-465
Number of pages11
JournalInternational immunology
Volume16
Issue number3
DOIs
Publication statusPublished - Mar 2004

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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    Ishihara, K., Sawa, S. I., Ikushima, H., Hirota, S., Atsumi, T., Kamimura, D., Park, S. J., Murakami, M., Kitamura, Y., Iwakura, Y., & Hirano, T. (2004). The point mutation of tyrosine 759 of the IL-6 family cytokine receptor gp130 synergizes with HTLV-1 pX in promoting rheumatoid arthritis-like arthritis. International immunology, 16(3), 455-465. https://doi.org/10.1093/intimm/dxh045