Wild-type FOXP3 is selectively active in CD4+CD25hi regulatory T cells of healthy female carriers of different FOXP3 mutations

Sara Di Nunzio, Massimiliano Cecconi, Laura Passerini, Alicia N. McMurchy, Udo Baron, Ivana Turbachova, Silvia Vignola, Erica Valencic, Alberto Tommasini, Anne Junker, Giantonio Cazzola, Sven Olek, Megan K. Levings, Lucia Perroni, Maria Grazia Roncarolo, Rosa Bacchetta

Research output: Contribution to journalArticlepeer-review

Abstract

Forkhead box P3 (FOXP3) is constitutively expressed by CD4 +CD25hi regulatory T cells (nTregs). Mutations of FOXP3 cause a severe autoimmune syndrome known as immune dysregulation polyendocrinopathy enteropathy X-linked, in which nTregs are absent or dysfunctional. Whether FOXP3 is essential for both differentiation and function of human nTreg cells remains to be demonstrated. Because FOXP3 is an X-linked gene subject to X-chromosome inactivation (XCI), we studied 9 healthy female carriers of FOXP3 mutations to investigate the role of wild-type (WT) versus mutated FOXP3 in different cell subsets. Analysis of active WT versus mutated (mut) - FOXP3 allele distribution revealed a random pattern of XCI in peripheral blood lymphocytes and in naive and memory CD4+ T cells, whereas nTregs expressed only the active WT-FOXP3. These data demonstrate that expression of WTFOXP3 is indispensable for the presence of a normal nTreg compartment and suggest that FOXP3 is not necessary for effector T-cell differentiation in humans.

Original languageEnglish
Pages (from-to)4138-4141
Number of pages4
JournalBlood
Volume114
Issue number19
DOIs
Publication statusPublished - Nov 5 2009

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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