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Blood, 5 November 2009, Vol. 114, No. 19, pp. 4138-4141. Prepublished online as a Blood First Edition Paper on September 8, 2009; DOI 10.1182/blood-2009-04-214593. This Article Full Text Full Text (PDF) Supplemental Methods and Table All Versions of this Article: blood-2009-04-214593v1 114/19/4138    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Di Nunzio, S. Articles by Bacchetta, R. PubMed PubMed Citation Articles by Di Nunzio, S. Articles by Bacchetta, R. Related Collections Immunobiology Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Brief report Wild-type FOXP3 is selectively active in CD4+CD25hi regulatory T cells of healthy female carriers of different FOXP3 mutations Sara Di Nunzio1,2, Massimiliano Cecconi3, Laura Passerini1, Alicia N. McMurchy4, Udo Baron5, Ivana Turbachova5, Silvia Vignola6, Erica Valencic7, Alberto Tommasini7, Anne Junker4, Giantonio Cazzola8, Sven Olek5, Megan K. Levings4, Lucia Perroni3, Maria Grazia Roncarolo1,9, and Rosa Bacchetta1 1 San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy; 2 University of Rome Tor Vergata, Rome, Italy; 3 Human Genetics Laboratory, Galliera Hospital, Genoa, Italy; 4 Department of Surgery, University of British Columbia, Vancouver, BC; 5 Epiontis GmbH, Berlin, Germany; 6 Pediatric Gastroenterology, Gaslini Hospital, Genoa, Italy; 7 Pediatric Immunology Laboratory, Istitutio di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofalo, Trieste, Italy; 8 Cystic Fybrosis Center, Verona, Italy; and 9 Vita Salute San Raffaele University, Milan, Italy 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 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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