1. A novel function for FOXP3 in humans: intrinsic regulation of conventional T cells.
- Author
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McMurchy, Alicia N., Gillies, Jana, Gizzi, Maria Concetta, Riba, Michela, Garcia-Manteiga, Jose Manuel, Cittaro, Davide, Lazarevic, Dejan, Di Nunzio, Sara, Piras, Ignazio S., Bulfone, Alessandro, Roncarolo, Maria Grazia, Stupka, Ella, Bacchetta, Rosa, and Levings, Megan K.
- Subjects
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T cells , *FORKHEAD transcription factors , *CYTOKINES , *GENE expression , *GENES - Abstract
The role of forkhead box P3 (FOXP3) is well-established in regulatory T cells, but the function of transient FOXP3 expression in activated human conventional T (Tconv) cells is unknown. We used two approaches to determine the role of FOXP3 in human Tconv cells. First, we obtained Tconv clones from a female 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 RNA against FOXP3. We found that FOXP3-deficient Tconv cells proliferate more, produce more cytokines than wild type Tconv cells, and have differential expression of 264 genes. We also investigated the role of FOXP3 in Th1 and Th17 cells and found that in comparison to Th1 cells, expression of activation-induced FOXP3 was higher and sustained in Th17 cells. Knocking down FOXP3 expression in Th17 cells significantly increased production of IFN-γ and decreased 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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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