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
Bloodjournal_title
Bloodauthors
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 Rdoi
10.1182/blood-2009-04-214593subject
Has Abstractpub_date
2009-11-05 00:00:00pages
4138-41issue
19eissn
0006-4971issn
1528-0020pii
blood-2009-04-214593journal_volume
114pub_type
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