title: Androgen receptor modulates Foxp3 expression in CD4+CD25+Foxp3+ regulatory T-cells.
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.
authors.affiliation: Department of Anatomy and Cell Biology, Pediatric Urology and Andrology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Walecki
authors.affiliation: Department of Anatomy and Cell Biology, Pediatric Urology and Andrology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Eisel
authors.affiliation: Department of Anatomy and Cell Biology, Pediatric Urology and Andrology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Klug
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Pediatric Urology and Andrology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
authors.forename: Nelli
authors.initials: N
authors.lastname: Baal
authors.affiliation: Department of Urology, Pediatric Urology and Andrology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Paradowska-Dogan
authors.affiliation: Department of Anatomy and Cell Biology, Pediatric Urology and Andrology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Wahle
authors.affiliation: Institute for Clinical Immunology and Transfusion Medicine, Pediatric Urology and Andrology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Hackstein
authors.affiliation: Department of Anatomy and Cell Biology, Pediatric Urology and Andrology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinhardt
authors.affiliation: 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.
authors.forename: Monika
authors.initials: M
authors.lastname: Fijak
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D051858:Forkhead Transcription Factors / Q000097:blood* / Q000235:genetics; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D011944:Receptors, Androgen / Q000097:blood* / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism*
chemical_list: C410798:AR protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D011944:Receptors, Androgen