IL-6 drives T cell proliferation
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《实验药学杂志》
Hyperresponsiveness to the IL-6 family of cytokines triggers a spontaneous rheumatoid arthritis (RA)-like disease in mice. On page 1459, Sawa and colleagues show that excessive IL-6 signaling drives hyperproliferation of CD4+ T cells, which then attack the joints.
IL-6 has been implicated in RA and other T cell–driven autoimmune diseases. Indeed, a previous study by this group showed that an activating mutation in the gp130 subunit of the IL-6 receptor caused a lymphocyte-driven arthritis in mice. But the mechanism was unclear. The authors now show that disease development in these mice depends on CD4+ T cells, but not on cytolytic CD8+ T cells or antibody-producing B cells.
The CD4+ cells did not appear to cause disease because of an affinity for joint-specific antigens. Rather, the cells simply proliferated excessively in the mutant mice. This hyperproliferation was not the fault of the T cell, as wild-type CD4+ T cells also multiplied excessively and caused disease when transferred into irradiated mutant mice.
Rather, the gp130 mutation caused nonhematopoietic cells to produce excess IL-7—a growth factor that triggers T cell proliferation. This is the first evidence that IL-6 family cytokines can trigger IL-7 production.
These data suggest that IL-6, which is elevated in the serum and joints of patients with RA, might exacerbate disease by inducing IL-7 and thus driving T cell activation. What causes the overstimulated T cells to attack the joints in the first place remains a mystery.
IL-6 has been implicated in RA and other T cell–driven autoimmune diseases. Indeed, a previous study by this group showed that an activating mutation in the gp130 subunit of the IL-6 receptor caused a lymphocyte-driven arthritis in mice. But the mechanism was unclear. The authors now show that disease development in these mice depends on CD4+ T cells, but not on cytolytic CD8+ T cells or antibody-producing B cells.
The CD4+ cells did not appear to cause disease because of an affinity for joint-specific antigens. Rather, the cells simply proliferated excessively in the mutant mice. This hyperproliferation was not the fault of the T cell, as wild-type CD4+ T cells also multiplied excessively and caused disease when transferred into irradiated mutant mice.
Rather, the gp130 mutation caused nonhematopoietic cells to produce excess IL-7—a growth factor that triggers T cell proliferation. This is the first evidence that IL-6 family cytokines can trigger IL-7 production.
These data suggest that IL-6, which is elevated in the serum and joints of patients with RA, might exacerbate disease by inducing IL-7 and thus driving T cell activation. What causes the overstimulated T cells to attack the joints in the first place remains a mystery.