FOXP1 is a regulator of quiescence in healthy human CD4+ T cells and is constitutively repressed in T cells from patients with lymphoproliferative disorders. Issue 1 (30th November 2016)

• Record Type: Journal Article
• 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
• Is Part Of: European journal of immunology. Volume 47:Issue 1(2017)
• Page Start: 168
• Page End: 179
• Publication Date: 2016-11-30
• Subjects: CD4+ T cells -- FOXP1 -- lymphocytic variant hypereosinophilic syndrome -- quiescence; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201646373
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract : FOXP1 is highly expressed in naïve human CD4 + T‐cells, repressed upon TCR activation and re‐established in memory cells. It is constitutionally repressed in peripheral T‐cell lymphoma (PTCL). Repression induces cell cycle entry, memory marker upregulation and differentiation gene expression. FOXP1 is important in human CD4 + T‐cell quiescence and PCTL development. 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.