Published online
doi:10.1084/jem.20062465
The Journal of Experimental Medicine, Vol. 204, No. 3, 475-480
The Rockefeller University Press, 0022-1007 $30.00
© Liston et al.
Lack of Foxp3 function and expression in the thymic epithelium
Adrian Liston1,
Andrew G. Farr1,2,
Zhibin Chen4,
Christophe Benoist4,
Diane Mathis4,
Nancy R. Manley5, and
Alexander Y. Rudensky1,3
1 Department of Immunology, 2 Department of Biological Structure, and 3 Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, WA 98195
4 Department of Medicine, Joslin Diabetes Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215
5 Department of Genetics, University of Georgia, Athens, GA 30602
CORRESPONDENCE Alexander Y. Rudensky: aruden{at}u.washington.edu
Foxp3 is essential for the commitment of differentiating thymocytes to the regulatory CD4+ T (T reg) cell lineage. In humans and mice with a genetic Foxp3 deficiency, absence of this critical T reg cell population was suggested to be responsible for the severe autoimmune lesions. Recently, it has been proposed that in addition to T reg cells, Foxp3 is also expressed in thymic epithelial cells where it is involved in regulation of early thymocyte differentiation and is required to prevent autoimmunity. Here, we used genetic tools to demonstrate that the thymic epithelium does not express Foxp3. Furthermore, we formally showed that genetic abatement of Foxp3 in the hematopoietic compartment, i.e. in T cells, is both necessary and sufficient to induce the autoimmune lesions associated with Foxp3 loss. In contrast, deletion of a conditional Foxp3 allele in thymic epithelial cells did not result in detectable changes in thymocyte differentiation or pathology. Therefore, in mice the only known role for Foxp3 remains promotion of T reg cell differentiation within the T cell lineage, whereas there is no role for Foxp3 in thymic epithelial cells.
Z. Chen's present address is Dept. of Microbiology and Immunology, University of Miami, Miami, FL 33136.

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