Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo

Zhou, Xuyu and Bailey-Bucktrout, Samantha L. and Jeker, Lukas T. and Penaranda, Cristina and Martínez-Llordella, Marc and Ashby, Meredith and Nakayama, Maki and Rosenthal, Wendy and Bluestone, Jeffrey A.. (2009) Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nature Immunology, 10 (9). pp. 1000-1007.

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Regulatory T cells (T(reg) cells) are central to the maintenance of immune homeostasis. However, little is known about the stability of T(reg) cells in vivo. In this study, we demonstrate that a substantial percentage of cells had transient or unstable expression of the transcription factor Foxp3. These 'exFoxp3' T cells had an activated-memory T cell phenotype and produced inflammatory cytokines. Moreover, exFoxp3 cell numbers were higher in inflamed tissues in autoimmune conditions. Adoptive transfer of autoreactive exFoxp3 cells led to the rapid onset of diabetes. Finally, analysis of the T cell receptor repertoire suggested that exFoxp3 cells developed from both natural and adaptive T(reg) cells. Thus, the generation of potentially autoreactive effector T cells as a consequence of Foxp3 instability has important implications for understanding autoimmune disease pathogenesis.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Molecular Immune Regulation (Jeker)
UniBasel Contributors:Jeker, Lukas T.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Dec 2020 10:48
Deposited On:16 Dec 2020 10:48

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