Lack of Foxp3 function and expression in the thymic epithelium

Adrian Liston, Andrew G. Farr, Zhibin Chen, Christophe Benoist, Diane Mathis, Nancy R. Manley, Alexander Y. Rudensky

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

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. JEM

Original languageEnglish
Pages (from-to)475-480
Number of pages6
JournalJournal of Experimental Medicine
Volume204
Issue number3
DOIs
StatePublished - Mar 19 2007

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Thymocytes
Epithelium
Epithelial Cells
Cell Lineage
T-Lymphocytes
Autoimmunity
Cell Differentiation
Alleles
Pathology
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Liston, A., Farr, A. G., Chen, Z., Benoist, C., Mathis, D., Manley, N. R., & Rudensky, A. Y. (2007). Lack of Foxp3 function and expression in the thymic epithelium. Journal of Experimental Medicine, 204(3), 475-480. https://doi.org/10.1084/jem.20062465

Lack of Foxp3 function and expression in the thymic epithelium. / Liston, Adrian; Farr, Andrew G.; Chen, Zhibin; Benoist, Christophe; Mathis, Diane; Manley, Nancy R.; Rudensky, Alexander Y.

In: Journal of Experimental Medicine, Vol. 204, No. 3, 19.03.2007, p. 475-480.

Research output: Contribution to journalArticle

Liston, A, Farr, AG, Chen, Z, Benoist, C, Mathis, D, Manley, NR & Rudensky, AY 2007, 'Lack of Foxp3 function and expression in the thymic epithelium', Journal of Experimental Medicine, vol. 204, no. 3, pp. 475-480. https://doi.org/10.1084/jem.20062465
Liston, Adrian ; Farr, Andrew G. ; Chen, Zhibin ; Benoist, Christophe ; Mathis, Diane ; Manley, Nancy R. ; Rudensky, Alexander Y. / Lack of Foxp3 function and expression in the thymic epithelium. In: Journal of Experimental Medicine. 2007 ; Vol. 204, No. 3. pp. 475-480.
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