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

X Zhou, SL Bailey-Bucktrout, LT Jeker… - Nature …, 2009 - nature.com
X Zhou, SL Bailey-Bucktrout, LT Jeker, C Penaranda, M Martínez-Llordella, M Ashby
Nature immunology, 2009nature.com
Regulatory T cells (Treg cells) are central to the maintenance of immune homeostasis.
However, little is known about the stability of Treg 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 …
Abstract
Regulatory T cells (Treg cells) are central to the maintenance of immune homeostasis. However, little is known about the stability of Treg 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 Treg cells. Thus, the generation of potentially autoreactive effector T cells as a consequence of Foxp3 instability has important implications for understanding autoimmune disease pathogenesis.
nature.com