HIRANO Toshio ≪Developmental Immunology≫ “ Autoimmune arthritis associated with mutated IL-6 receptor gp130 is driven by STAT3/IL-7-dependent homeostatic proliferation of CD4+ T cells”
Publish J. Exp. Med. 203:1459-1470, 2006
Mice with F759 mutation in IL-6 receptor gp130 have enhanced STAT3 activation and spontaneously developed a rheumatoid arthritis-like joint disease. Here, we show that the disease development is dependent on both CD4+ T cells and IL-6 family cytokines. In spite of the necessity for CD4+ T cells, the gp130 mutation was only required in nonhemtopoietic cells for the disease induction. The gp130 mutation in nonhemtopoietic cells enhanced production of IL-7. Conditional knockout of STAT3 in nonlymphoid cells ablated the enhanced production of IL-7. Homeostatic proliferation (HP) of CD4+ T cells was enhanced in gp130 mutant mice. Acceleration of the HP enhanced the disease. Anti-IL-7 antibody treatment inhibited not only the enhanced HP, but also the disease in gp130 mutant mice. Our results show that autoimmune disease in gp130 mutant mice is caused by increased HP of CD4+ T cells, which is due to elevated production of IL-7 by nonhematopoietic cells as a result of dysregulated-gp130-STAT3 signaling.