ESTRIOL EFFECT ON PROLIFERATIVE ACTIVITY OF REGULATORY THYMOCYTE SUBPOPULATIONS



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Abstract

Abstract

Steroid hormone estriol (E3), synthesized by fetoplacental unit, effectively regulates reproductive tissues and immune cells functioning. One of the key mechanisms for maintaining immunological tolerance during gestation is a shift in regulatory lymphocytes subgroups ratio – IL-17-producing cells (Th17) and regulatory T cells (Treg). Invariant natural killer T cells (iNKT), which have both cytotoxic and immunoregulatory activity, also play an important role during pregnancy. Differentiation of these lymphocyte subtypes begins in the thymus. The aim of the work was to study E3 effect on the thymic regulatory cells subpopulation composition (Th17, Treg, iNKT) in vitro. Thymocytes were cultured for 72 h with E3 at a concentration of 20 ng/ml, characterizing its maximum level in the peripheral blood during pregnancy, with CD3/CD28 particles, and then regulatory cells subpopulation composition and Ki-67 expression in them were assessed by flow cytometry. Thymic nTreg cells were defined as CD4+CD25+FoxP3+ cells percentage; Th17 cells were estimated as CD4+IL-17A+RORγt+ cells percentage; iNKT cells were determined as CD3hiVa24Ja18+ cells percentage in thymocyte culture. Treg, Th17, and iNKT proliferative potential was estimated by Ki-67 expression. E3 inhibited stimulated by CD3/CD28 thymocytes differentiation towards nTreg and enhanced iNKT formation. The hormone had no significant effect on Ki-67+ nTreg and iNKT cells number, but there was a tendency to decrease. E3 did not affect Th17 number but inhibited its proliferative response. Thus, E3 changes its classical effect to the opposite in the presence of an antigen, protecting mother's body from potential danger. The hormone enhanced iNKT formation and inhibited nTreg formation from thymocytes. At the same time, E3 negatively regulated thymic Th17 cells proliferation, compensating for nTreg number decrease and preventing premature birth possibility. Since pregnancy is known to be accompanied by steroid-induced thymus atrophy, we have demonstrated one of the possible mechanisms underlying this process, involving the pregnancy hormone E3.

About the authors

Irina Valerievna Nekrasova

Institute of Ecology and Genetic of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences, Perm, Russian Federation

Email: nirina5@mail.ru
ORCID iD: 0000-0002-6706-5912
SPIN-code: 8706-1904
Scopus Author ID: 36900532300
ResearcherId: E-8242-2016

PhD, researcher, laboratory of immunoregulation

Russian Federation, 13, Golev street, Perm, 614081

Olga Aleksandrovna Loginova

Institute of Ecology and Genetic of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences, Perm, Russian Federation

Email: jallopukki@ya.ru
ORCID iD: 0000-0001-6050-8656
SPIN-code: 9610-3514
Scopus Author ID: 56728157800
ResearcherId: T-6042-2017

PhD, junior researcher, laboratory of immunoregulation

Russian Federation, 13,Golev street, Perm, 614081

Ekaterina Grigorievna Orlova

Institute of Ecology and Genetic of Microorganisms, Perm Federal Research Center, Ural Branch, Russian Academy of Sciences, Perm, Russian Federation

Author for correspondence.
Email: orlova_katy@mail.ru
ORCID iD: 0000-0003-1195-8962
SPIN-code: 7707-1076
Scopus Author ID: 7103163971
ResearcherId: D-8782-2017

Doctor of biology, leading researcher, laboratory of immunoregulation

Russian Federation, 13, Golev street, Perm, 614081

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