Wild-type FOXP3 is selectively active in CD4+CD25(hi) regulatory T cells of healthy female carriers of different FOXP3 mutations.

Abstract:

:Forkhead box P3 (FOXP3) is constitutively expressed by CD4(+)CD25(hi) 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 WT-FOXP3 is indispensable for the presence of a normal nTreg compartment and suggest that FOXP3 is not necessary for effector T-cell differentiation in humans.

journal_name

Blood

journal_title

Blood

authors

Di Nunzio S,Cecconi M,Passerini L,McMurchy AN,Baron U,Turbachova I,Vignola S,Valencic E,Tommasini A,Junker A,Cazzola G,Olek S,Levings MK,Perroni L,Roncarolo MG,Bacchetta R

doi

10.1182/blood-2009-04-214593

subject

Has Abstract

pub_date

2009-11-05 00:00:00

pages

4138-41

issue

19

eissn

0006-4971

issn

1528-0020

pii

blood-2009-04-214593

journal_volume

114

pub_type

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