Description
FoxP3 is a central regulator of immunological tolerance, controlling the development and function of regulatory T (Treg) cells. To dissect the complex processes orchestrated by FoxP3, we investigated impacts of three autoimmune disease-associated missense FoxP3 mutations in mice. The I363V and R397W mutations were loss-of-function mutations, causing multi-organ inflammation by globally compromising Treg cell physiology. By contrast, the A384T mutation induced a distinctive tissue-restricted inflammation by specifically impairing the ability of Treg cells to compete with pathogenic T cells in certain non-lymphoid tissues.