title: Enhanced generation of suppressor T cells in patients with asthma taking oral contraceptives.
abstract: Introduction. A dysregulation of regulatory T cells (Tregs) could play a major role in the pathogenesis of bronchial asthma. Sex-dependent differences as well as the impact of hormonal changes in the incidence and severity of asthma are widely recognized. Emerging evidence suggests that asthma symptoms are alleviated in female patients taking hormone oral contraceptives (OCs). The impact of OCs on the generation of induced Tregs (iTregs) was assessed in a cohort of female patients with asthma. Methods. Thirteen patients were included in this pilot study. During three distinct phases of their menstrual cycles, we measured exhaled nitric oxide (eNO) levels, forced expiratory volume at 1 second (FEV1s), asthma control test (ACT) score, sex steroid hormone levels in serum, natural Tregs in peripheral blood, and the ability of CD4(+) T cells to generate iTregs ex vivo. Results. The luteal serum levels of estradiol and progesterone negatively correlated with the proportion of iTregs generated ex vivo in patients not taking OCs. In addition, physiological doses of estradiol and progesterone prevented the acquisition of a suppressor T cell phenotype in vitro. Interestingly, patients taking OCs had reduced serum sex hormone levels associated with higher iTreg induction, a better ACT score, and a tendency toward lower eNO levels. Conclusions. Our results identify an impact of sex hormones on the capacity of T cells to polarize towards a regulatory phenotype and suggest the regulation of peripheral T cell lineage plasticity as a potential mechanism underlying the beneficial effects of OCs in women with asthma.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, Chandler Medical Center, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
authors.forename: A Catalina
authors.initials: AC
authors.lastname: Vélez-Ortega
authors.forename: James
authors.initials: J
authors.lastname: Temprano
authors.forename: Mary Catherine
authors.initials: MC
authors.lastname: Reneer
authors.forename: Gavin I
authors.initials: GI
authors.lastname: Ellis
authors.forename: Andrea
authors.initials: A
authors.lastname: McCool
authors.forename: Tonya
authors.initials: T
authors.lastname: Gardner
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khosravi
authors.forename: Francesc
authors.initials: F
authors.lastname: Marti
mesh_terms: D000328:Adult; D001249:Asthma / Q000097:blood / Q000276:immunology*; D001944:Breath Tests; D015331:Cohort Studies; D003276:Contraceptives, Oral / Q000494:pharmacology*; D004958:Estradiol / Q000097:blood / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000276:immunology; D006801:Humans; D008597:Menstrual Cycle / Q000187:drug effects / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology; D010865:Pilot Projects; D011374:Progesterone / Q000097:blood / Q000276:immunology; D018709:Statistics, Nonparametric; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D055815:Young Adult
chemical_list: D003276:Contraceptives, Oral; D009569:Nitric Oxide; D011374:Progesterone; D004958:Estradiol