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Mol Biol Cell. 2015 Aug 1;26(15):2845-57. doi: 10.1091/mbc.E14-08-1323. Epub 2015 Jun 10.

Androgen receptor modulates Foxp3 expression in CD4+CD25+Foxp3+ regulatory T-cells.

Author information

1
Department of Anatomy and Cell Biology, Pediatric Urology and Andrology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
2
Institute for Clinical Immunology and Transfusion Medicine, Pediatric Urology and Andrology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
3
Department of Urology, Pediatric Urology and Andrology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
4
Department of Anatomy and Cell Biology, Pediatric Urology and Andrology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany monika.fijak@anatomie.med.uni-giessen.de.

Abstract

CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells are able to inhibit proliferation and cytokine production in effector T-cells and play a major role in immune responses and prevention of autoimmune disease. A master regulator of Treg cell development and function is the transcription factor Foxp3. Several cytokines, such as TGF-β and IL-2, are known to regulate Foxp3 expression as well as methylation of the Foxp3 locus. We demonstrated previously that testosterone treatment induces a strong increase in the Treg cell population both in vivo and in vitro. Therefore we sought to investigate the direct effect of androgens on expression and regulation of Foxp3. We show a significant androgen-dependent increase of Foxp3 expression in human T-cells from women in the ovulatory phase of the menstrual cycle but not from men and identify a functional androgen response element within the Foxp3 locus. Binding of androgen receptor leads to changes in the acetylation status of histone H4, whereas methylation of defined CpG regions in the Foxp3 gene is unaffected. Our results provide novel evidence for a modulatory role of androgens in the differentiation of Treg cells.

PMID:
26063731
PMCID:
PMC4571343
DOI:
10.1091/mbc.E14-08-1323
[Indexed for MEDLINE]
Free PMC Article

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