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

被引：1028

作者：

Zhou, Xuyu ^{[1
,2
]}

Bailey-Bucktrout, Samantha L. ^{[1
,2
]}

Jeker, Lukas T. ^{[1
,2
]}

Penaranda, Cristina ^{[1
,2
]}

Martinez-Llordella, Marc

Ashby, Meredith ^{[1
,2
]}

Nakayama, Maki ^{[3
]}

Rosenthal, Wendy ^{[1
,2
]}

Bluestone, Jeffrey A. ^{[1
,2
]}

机构：

[1] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[3] Univ Colorado, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA

来源：

NATURE IMMUNOLOGY | 2009年 / 10卷 / 09期

基金：

美国国家卫生研究院; 瑞士国家科学基金会;

关键词：

DNA METHYLATION; GENE-EXPRESSION; REG-CELLS; LINEAGE; POLYENDOCRINOPATHY; DIFFERENTIATION; AUTOIMMUNITY; ENTEROPATHY; HOMEOSTASIS; DISRUPTION;

D O I：

10.1038/ni.1774

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1000 / U104

页数：9

共 39 条

[1] The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3 [J].