FOXP1 is a regulator of quiescence in healthy human CD4<sup>+sup> T cells and is constitutively repressed in T cells from patients with lymphoproliferative disorders

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• 作者：Soizic Garaud ; Florence Roufosse ; Pushpamali De Silva ; Chunyan Gu-Trantien ; Jean-Nicolas Lodewyckx ; Hugues Duvillier ; Sarah Dedeurwaerder ; Martin Bizet ; Matthieu Defrance ; Franç ; ois Fuks ; Franç ; oise Bex and Karen Willard-Gallo
• 刊名：European Journal of Immunology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：47
• 期：1
• 页码：168-179
• 全文大小：1696K
• ISSN：1521-4141

文摘

The forkhead box P1 (FOXP1) transcription factor has been shown to regulate the generation and maintenance of quiescent naïve murine T cells. In humans, FOXP1 expression has been correlated with overall survival in patients with peripheral T-cell lymphoma (PTCL), although its regulatory role in T-cell function is currently unknown. We found that FOXP1 is normally expressed in all human leukocyte subpopulations. Focusing on primary human CD4<sup>+sup> T cells, we show that nuclear expression of FOXP1 predominates in naïve cells with significant downregulation detected in memory cells from blood and tonsils. FOXP1 is repressed following in vitro T-cell activation of naïve T cells, and later re-established in memory CD4<sup>+sup> T cells, albeit at lower levels. DNA methylation analysis revealed that epigenetic mechanisms participate in regulating the human FOXP1 gene. ShRNA-mediated FOXP1 repression induces CD4<sup>+sup> T cells to enter the cell cycle, acquire memory-like markers and upregulate helper T-cell differentiation genes. In patients with lymphoproliferative disorders, FOXP1 expression is constitutionally repressed in the clonal T cells in parallel with overexpression of helper T-cell differentiation genes. Collectively, these data identify FOXP1 as an essential transcriptional regulator for primary human CD4<sup>+sup> T cells and suggest its potential important role in the development of PTCL.