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

Research output: Contribution to journalArticle

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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 1 2004

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Cytokine Receptor gp130
Human T-lymphotropic virus 1
Point Mutation
Arthritis
Tyrosine
Rheumatoid Arthritis
Transgenic Mice
Interleukin-6
Splenomegaly
Incidence
Autoimmunity
Granulocytes
Autoantibodies
Autoimmune Diseases
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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

In: International Immunology, Vol. 16, No. 3, 01.03.2004, p. 455-465.

Research output: Contribution to journalArticle

Ishihara, K, Sawa, SI, Ikushima, H, Hirota, S, Atsumi, T, Kamimura, D, Park, SJ, 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, vol. 16, no. 3, pp. 455-465. https://doi.org/10.1093/intimm/dxh045
Ishihara, Katsuhiko ; Sawa, Shin Ichiro ; Ikushima, Hideto ; Hirota, Seiichi ; Atsumi, Toru ; Kamimura, Daisuke ; Park, Sung Joo ; Murakami, Masaaki ; Kitamura, Yukihiko ; Iwakura, Yoichiro ; Hirano, Toshio. / 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. In: International Immunology. 2004 ; Vol. 16, No. 3. pp. 455-465.
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