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, 16 (3), 455-65

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

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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

Katsuhiko Ishihara et al. Int Immunol.

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-gamma-globulinemia, autoantibody production, increases in memory/activated T cells and granulocytes in the peripheral lymphoid organs, and a decrease in the class II MHC(bright) 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.

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