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
Copyright policy )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
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.
- Osaka University Japan
- RIKEN Japan
- University of Tokyo Japan
Human T-lymphotropic virus 1, Membrane Glycoproteins, Interleukin-6, Genes, pX, Flow Cytometry, Arthritis, Rheumatoid, Mice, Inbred C57BL, Radiography, Disease Models, Animal, Mice, Antigens, CD, T-Lymphocyte Subsets, Cytokine Receptor gp130, Animals, Point Mutation, Tyrosine, Myeloid Cells, Lymph Nodes, Ankle Joint, Spleen
Human T-lymphotropic virus 1, Membrane Glycoproteins, Interleukin-6, Genes, pX, Flow Cytometry, Arthritis, Rheumatoid, Mice, Inbred C57BL, Radiography, Disease Models, Animal, Mice, Antigens, CD, T-Lymphocyte Subsets, Cytokine Receptor gp130, Animals, Point Mutation, Tyrosine, Myeloid Cells, Lymph Nodes, Ankle Joint, Spleen
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