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- Title
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.
- Authors
Garaud, Soizic; Roufosse, Florence; De Silva, Pushpamali; Gu‐Trantien, Chunyan; Lodewyckx, Jean‐Nicolas; Duvillier, Hugues; Dedeurwaerder, Sarah; Bizet, Martin; Defrance, Matthieu; Fuks, François; Bex, Françoise; Willard‐Gallo, Karen
- Abstract
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+ 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+ 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+ 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+ T cells and suggest its potential important role in the development of PTCL.
- Publication
European Journal of Immunology, 2017, Vol 47, Issue 1, p168
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201646373