FoxP3 (red) is expressed on cortical epithelial cells (green) and drives thymocyte proliferation.

On page 1141, the one-trick transcription factor FoxP3 reveals a new function. According to Chang and colleagues, FoxP3 does more than just drive regulatory T (T reg) cell development; it also promotes the proliferation of developing thymocytes.

FoxP3 is required for the development of CD4+CD25+ T reg cells, which subdue the activation of conventional T cells and thus protect against chronic inflammation and autoimmunity. Mice and humans that lack FoxP3 develop a spontaneous, multi-organ autoimmune disease that has been primarily attributed to the lack of T reg cells. But one fact suggests that this explanation may be too simple. Irradiated mice that are reconstituted with FoxP3-deficient bone marrow do not develop disease, suggesting that FoxP3 also functions in nonhematopoietic cells.

Chang and colleagues now show that FoxP3 is not exclusive to T cells, but is also expressed in thymic epithelial cells. In mice lacking FoxP3, developing thymocytes were unable to proliferate normally, resulting in thymic atrophy. The proliferation defect was caused by a lack of FoxP3 in thymic stromal cells, rather than in T cells, as normal thymocytes also failed to proliferate in a FoxP3-deficient thymic environment.How FoxP3 expression on thymic epithelial cells helps drive thymocyte proliferation is unknown. Also unclear is how the proliferation defect contributes to autoimmune disease, although there is a long-standing but poorly understood link between thymic atrophy and T cell–driven autoimmune disease.