Anovel function for FOXP3 in humans: Intrinsic regulation of conventional T cells

Alicia N. McMurchy, Jana Gillies, Maria Concetta Gizzi, Michela Riba, Jose Manuel Garcia-Manteiga, Davide Cittaro, Dejan Lazarevic, Sara Di Nunzio, Ignazio S. Piras, Alessandro Bulfone, Maria Grazia Roncarolo, Elia Stupka, Rosa Bacchetta, Megan K. Levings

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1265-1275
Number of pages11
JournalBlood
Volume121
Issue number8
DOIs
Publication statusPublished - Feb 21 2013

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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    McMurchy, A. N., Gillies, J., Gizzi, M. C., Riba, M., Garcia-Manteiga, J. M., Cittaro, D., Lazarevic, D., Di Nunzio, S., Piras, I. S., Bulfone, A., Roncarolo, M. G., Stupka, E., Bacchetta, R., & Levings, M. K. (2013). Anovel function for FOXP3 in humans: Intrinsic regulation of conventional T cells. Blood, 121(8), 1265-1275. https://doi.org/10.1182/blood-2012-05-431023