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Foxp3 deletion in T cells (CD4-Cre) but not thymic epithelial cells (Foxn1-Cre) causes an autoimmune wasting disease.
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Liston et al. (page 475) report that a transcription factor that protects mice against autoimmunity is required for regulatory T cell (T reg) function only, and not for thymic epithelial cell function, as previously reported.
Mutations in the Foxp3 gene have been identified as the basis of autoimmune syndromes in both mice and men. This was thought to be due to a failure in the development of immune-suppressing T reg cells, which has been shown to require Foxp3.
However, a recent study indicated that Foxp3-lacking bone marrow cells do not cause autoimmunity when transferred into mice that lack T cells but express Foxp3 in their thymic stroma (JEM 202:1141). This suggested that Foxp3 also functioned in non–T cells, and that the autoimmunity suffered by Foxp3-deficient animals might be due not to defective T regs but to a defective thymic epithelium.
To Liston et al., a function for Foxp3 outside of T regs sounded suspicious, as Foxp3 had previously been extensively characterized as being specific to T regs. They have now specifically deleted Foxp3 in T cells. This targeted deletion caused the same full-blown autoimmunity as seen in Foxp3-negative mice. The deletion of Foxp3 in the non–T cell populations of the thymus, however, did not cause disease.
The authors also show that, in normal mice, Foxp3 is not expressed in thymic epithelia but is limited to T reg cells alone. Although these results redefine Foxp3 expression, the reason for the disparity between the two papers remains unclear. 
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