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

First Author  Zhou X Year  2009
Journal  Nat Immunol Volume  10
Issue  9 Pages  1000-7
PubMed ID  19633673 Mgi Jnum  J:275828
Mgi Id  MGI:6304027 Doi  10.1038/ni.1774
Citation  Zhou X, et al. (2009) Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Nat Immunol 10(9):1000-7
abstractText  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.
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