期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 47, 期 1, 页码 168-179出版社
WILEY
DOI: 10.1002/eji.201646373
关键词
CD4(+) T cells; FOXP1; lymphocytic variant hypereosinophilic syndrome; quiescence
类别
资金
- Belgian Fund for Scientific Research (FNRS)
- FNRS-Operation Televie
- Les Amis de l'Institut Bordet
- Medic Foundation
- Plan Cancer of Belgium
- Fonds J.C. Heuson
- Fonds Lambeau-Marteaux
The forkhead box P1 (FOXP1) transcription factor has been shown to regulate the generation and maintenance of quiescent naive 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 naive cells with significant downregulation detected in memory cells from blood and tonsils. FOXP1 is repressed following in vitro T-cell activation of naive 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.
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