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Magg, T.* ; Mannert, J.* ; Ellwart, J.W. ; Schmid, I.* ; Albert, M.H.*

Subcellular localization of FOXP3 in human regulatory and nonregulatory T cells.

Eur. J. Immunol. 42, 1627-1638 (2012)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The transcriptional regulator FOXP3 is an important determinant of regulatory T (Treg) cell development and function and is frequently used to quantitate Treg cells. However, FOXP3 is also expressed in recently activated conventional human T cells. Here, we investigated the FOXP3 expression patterns in Treg and activated T cells at a cellular level. Upon activation, human CD4+CD25- T cells expressed FOXP3 mainly in the cytoplasm, in sharp contrast to human CD4+CD25+ Treg cells, where we found FOXP3 to be predominantly expressed in the nucleus. A GFP-FOXP3-fusion protein shuttled from the nucleus to the cytoplasm in transfected primary human T cells. We identified two novel leucine-rich nuclear export signals in FOXP3. Site-directed mutagenesis of both sequences completely abolished nuclear export of FOXP3 in human T cells. Both export sequences localized to exons affected by alternative splicing. The three isoforms FOXP3?2, FOXP3?7, and FOXP3?2?7 localized preferentially to the nucleus. Additionally, forced expression of nucleus-directed FOXP3 induced a Treg-cell-associated gene expression pattern and induced regulatory capacity. These findings should aid in the interpretation of future studies utilizing FOXP3 expression as a Treg-cell marker and shed some light on the molecular mechanisms controlling subcellular FOXP3 localization in human T cells.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Activated T Cell; Foxp3; Nuclear-cytoplasmic Shuttling; Treg Cell; TRANSCRIPTION FACTOR FOXP3; NUCLEAR EXPORT SIGNALS; GENE-EXPRESSION; HUMAN-DISEASES; ACTIVATION; GENERATION; TOLERANCE; PROLIFERATION; SUBPOPULATION; REPRESSOR
ISSN (print) / ISBN 0014-2980
e-ISSN 1521-4141
Journal European Journal of Immunology
Quellenangaben Volume: 42, Issue: 6, Pages: 1627-1638 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)