par 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 
Référence European Journal of Immunology, 47, 1, page (168-179)
Publication Publié, 2017-01










Référence European Journal of Immunology, 47, 1, page (168-179)
Publication Publié, 2017-01
Article révisé par les pairs
Résumé : | 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. |