A novel function for FOXP3 in humans: intrinsic regulation of conventional T cells.
Blood, 2013/2/21;121(8):1265-75.
McMurchy AN[1], Gillies J, Gizzi MC, Riba M, Garcia-Manteiga JM, Cittaro D, Lazarevic D, Di Nunzio S, Piras IS, Bulfone A, Roncarolo MG, Stupka E, Bacchetta R, Levings MK
Affiliations
PMID: 23169781DOI: 10.1182/blood-2012-05-431023
Impact factor: 25.476
Abstract
The role of forkhead box P3 (FOXP3) is well-established in T-regulatory cells, but the function of transient FOXP3 expression in activated human conventional T (Tconv) cells is unknown. In the present study, we used 2 approaches to determine the role of FOXP3 in human Tconv cells. First, we obtained Tconv clones from a female subject who is hemizygous for a null mutation in FOXP3, allowing the comparison of autologous T-cell clones that do or do not express FOXP3. Second, we knocked down activation-induced FOXP3 in Tconv cells from healthy donors with small interfering RNAagainst FOXP3. We found that FOXP3-deficient Tconv cells proliferate more and produce more cytokines than wild-type Tconv cells and have differential expression of 274 genes. We also investigated the role of FOXP3 in Th1 and Th17 cells and found that the expression of activation-induced FOXP3 was higher and more sustained in Th17 cells compared with Th1 cells. Knocking down FOXP3 expression in Th17 cells significantly increased the production of IFN-γ and decreased the expression of CCR4, but had no effect on IL-17 expression. These data reveal a novel function of FOXP3 in Tconv cells and suggest that expression of this protein is important in the function of multiple CD4(+) T-cell lineages.
MeSH terms
CD4-Positive T-Lymphocytes; Cell Lineage; Cell Proliferation; Clone Cells; Female; Forkhead Transcription Factors; Gene Expression Regulation; Humans; Interferon-gamma; Interleukin-2; Male; RNA, Small Interfering; Receptors, CCR4; Th1 Cells; Th17 Cells; Transcriptome
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