Receptors against autoimmunity

Men are less prone to autoimmunity than women thanks to the anti-inflammatory effect of male sex hormones. But how these androgens, such as testosterone, exert this effect was a mystery. Dunn and colleagues now report on page 321 that a nuclear hormone receptor that gets boosted by testosterone switches off pro-inflammatory cytokine production in male CD4⁺ T cells.

Androgens are known to shift the balance from pro-inflammatory Th1 cytokines to anti-inflammatory Th2 cytokines. Thus, a testosterone shot is all it takes to suppress lupus and diabetes symptoms in mice. “The link between androgens and protection against autoimmunity could not be clearer,” says senior author Larry Steinman. “But we still had to figure out how androgens actually instruct T cells to stop attacking the host.”

A good candidate was the nuclear...