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Distinct regulatory roles of transforming growth factor-beta and interleukin-4 in the development and maintenance of natural and induced CD4+ CD25+ Foxp3+ regulatory T cells
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SYSNO ASEP 0333972 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Distinct regulatory roles of transforming growth factor-beta and interleukin-4 in the development and maintenance of natural and induced CD4+ CD25+ Foxp3+ regulatory T cells Author(s) Procházková, Jana (UMG-J)
Frič, Jan (UMG-J)
Pokorná, Kateřina (UMG-J)
Neuwirth, Aleš (UMG-J) ORCID
Krulová, Magdalena (UMG-J)
Zajícová, Alena (UMG-J)
Holáň, Vladimír (UMG-J)Number of authors 7 Source Title Immunology - ISSN 0019-2805
Roč. 128, 1 Suppl (2009), e670-e678Number of pages 9 s. Language eng - English Country GB - United Kingdom Keywords alloantigen ; cytokines ; suppression Subject RIV EB - Genetics ; Molecular Biology R&D Projects KAN200520804 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR) GD310/08/H077 GA ČR - Czech Science Foundation (CSF) 1M0506 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) CEZ AV0Z50520514 - UMG-J (2005-2011) UT WOS 000268703800052 DOI 10.1111/j.1365-2567.2009.03060.x Annotation The development and function of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are strictly regulated by cytokines. Here we show that TGF-b and IL-4 play a crucial and antagonistic role in the development of Tregs and have distinct effects on maintenance of natural (nTregs) and antigen-induced (iTregs) Tregs. We demonstrated that CD4+CD25+Foxp3+ iTregs develop upon alloantigenic stimulation in the presence of TGF-b exclusively from CD4+CD25-Foxp3- precursors. Both induction of Foxp3 expression and Treg proliferation were prevented when the cells were stimulated in the presence of IL-4. IL-4 decreased the number of Foxp3+ cells in a population of iTregs while it substantially supported the survival of nTregs. iTregs inhibit cell proliferation comparably to nTregs and their suppressive capacity is not modulated by IL-4. These data suggest that TGF-b and IL-4 differentially regulate the development and maintenance of Tregs but have no influence on the suppressive activity of Tregs. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2010
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