mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-COT-2990mimmun-2990Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESИзменения функционального фенотипа циркулирующих моноцитов в динамике беременностиСhanges of the functional phenotype of circulating monocytes during pregnancyБухтуеваН. Г.BukhtuevaN. G.

Бухтуева Н.Г. – врач – акушер-гинеколог акушерского обсервационного отделения № 1

г. Новосибирск

Bukhtueva N.G., Obstetrician-Gynecologist, Obstetric Observational Department No. 1

Novosibirsk

ct_lab@mail.ruЛеплинаО. Ю.LeplinaO. Yu.

Леплина Ольга Юрьевна – д.м.н., ведущий научный сотрудник лаборатории клеточной иммунотерапиис

630099, г. Новосибирск, ул. Ядринцевская, 14

Тел.: 8 (383) 228-21-01

Факс: 8 (383) 222-70-28

Olga Yu. Leplina, PhD, MD (Medicine), Leading Research Associate, Laboratory of Cellular Immunotherapy

14 Yadrintsevskaya St Novosibirsk 630099 

Phone: +7 (383) 228-21-01

Fax: +7 (383) 222-70-28

oleplina@mail.ruШевелаЕ. Я.ShevelaE. Ya.

Шевела Е.Я. – д.м.н., ведущий научный сотрудник лаборатории клеточной иммунотерапии

г. Новосибирск

Shevela E.Ya., PhD, MD (Medicine), Leading Research Associate, Laboratory of Cellular Immunotherapy

Novosibirsk

shevelak@mail.ruТихоноваМ. А.TikhonovaM. A.

Тихонова М.А. – к.б.н., старший научный сотрудник лаборатории клеточной иммунотерапии

г. Новосибирск 

Tikhonova M.A., PhD (Biology), Senior Research Associate, Laboratory of Cellular Immunotherapy

Novosibirsk

martix-59@mail.ruПасманН. М.PasmanN. M.

Пасман Н.М. – д.м.н., профессор, заведующая кафедрой акушерства и гинекологии, Институт медицины и психологии

г. Новосибирск

Pasman N.М., PhD, MD (Medicine), Professor, Head, Department of Obstetrics and Gynecology of Institute ofMedicine and Psychology

Novosibirsk

ct_lab@mail.ruОстанинА. А.OstaninA. A.

Останин А.А. – д.м.н., профессор, главный научный сотрудник лаборатории клеточной иммунотерапии

г. Новосибирск

Ostanin A.A., PhD, MD (Medicine), Professor, Chief Research Associate, Laboratory of Cellular Immunotherapy

Novosibirsk

ostanin62@mail.ruЧерныхЕ. Р.ChernykhE. R.

Черных Е.Р. – д.м.н., профессор, член-корр. РАН, заведующая лабораторией клеточной иммунотерапии

г. Новосибирск

Chernykh E.R., PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Head, Laboratory of Cellular Immunotherapy

Novosibirsk

ct_lab@mail.ruГБУЗ НСО «Городская больница № 1»РоссияCity Hospital No. 1Russian FederationФГБНУ «Научно-исследовательский институт фундаментальной и клинической иммунологии»РоссияResearch Institute of Fundamental and Clinical ImmunologyRussian FederationИнститут медицины и психологии ФГАОУ ВО «Новосибирский национальный исследовательский государственный университет»РоссияInstitute of Medicine and Psychology, Novosibirsk National Research State UniversityRussian Federation202508012025271179196Copyright © Бухтуева Н.Г., Леплина О.Ю., Шевела Е.Я., Тихонова М.А., Пасман Н.М., Останин А.А., Черных Е.Р., 20252025Бухтуева Н.Г., Леплина О.Ю., Шевела Е.Я., Тихонова М.А., Пасман Н.М., Останин А.А., Черных Е.Р.Bukhtueva N.G., Leplina O.Y., Shevela E.Y., Tikhonova M.A., Pasman N.M., Ostanin A.A., Chernykh E.R.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2990

Перестройка иммунной системы при беременности представляет строго контролируемый динамический процесс, в рамках которого первый и третий триместр являются провоспалительными, а второй – соответствует противовоспалительной фазе. Однако вовлеченность моноцитов в регуляцию баланса между воспалительным и противовоспалительным статусом остается мало изученной. Известно, что функциональный фенотип моноцитов зависит от их субпопуляционной принадлежности, оцениваемой по экспрессии CD14 и СD16, и сопряжен с экспрессией М1(CCR2)- и М2(CD206)- ассоциированных молекул, характеризующих, соответственно, моноциты с про- и противовоспалительной активностью. В настоящей работе методом проточной цитофлюориметрии исследована экспрессия CCR2 и CD206 в субпопуляциях классических (CD14++CD16- , кМо), промежуточных (CD14++CD16+, пМо) и неклассических (CD14+CD16++, нМо) моноцитов у беременных на различных сроках гестации в сравнении с небеременными. В исследование были включены 14 беременных в первом, 20 – во втором и 26 – в третьем триместре, а также 29 фертильных небеременных. Однофакторный дисперсионный анализ выявил существенные различия в экспрессии CCR2 и CD206 в указанных группах, которые были наиболее выражены в классических и промежуточных моноцитах и сильнее проявлялись в отношении экспрессии CD206. В целом моноциты беременных характеризовались сниженной экспрессией CCR2 и повышенной экспрессией CD206, что свидетельствовало о смещении баланса в сторону противовоспалительного профиля. Эти изменения проявлялись уже в первом триместре (повышенный уровень средней интенсивности флюоресценции [MFI] CD206 в кМо и пМо; p < 0,05) и достигали наибольшей выраженности во втором триместре, проявляясь достоверно повышенной экспрессией CD206 (% клеток, MFI) и сниженной экспрессией CCR2 (% клеток, MFI) во всех субпопуляциях моноцитов. В третьем триместре доля CD206+ кМо по сравнению со вторым триместром снижалась (p < 0,05), а относительное содержание CCR2+ клеток в кМо и пМо повышалось. Характерно, что в первом и третьем триместрах выявленные изменения сочетались с усилением провоспалительного профиля моноцитов, которое в первом триместре было рестриктировано субпопуляцией неклассических моноцитов, а в третьем триместре опосредовалось промежуточными и неклассическими моноцитами. Полученные данные свидетельствуют о вовлеченности моноцитов в регуляцию про- и противовоспалительного баланса в динамике гестации с преобладающим формированием М2-профиля в классических моноцитах в первом и третьем триместрах и всех субпопуляциях моноцитов во 2-м триместре и усилением М1-провоспалительного профиля в промежуточных и неклассических моноцитах в первом и третьем триместрах.

Rearrangement of the immune system during pregnancy is a strictly controlled, dynamic process in which the first and third trimesters are, respectively, pro-inflammatory, and anti-inflammatory periods. However, monocyte involvement in regulating the pro/anti-inflammatory balance remains poorly understood. The functional phenotype of monocytes is known to depend on their subsets assessed by CD14 and CD16 expression, and is associated with expression of M1(CCR2)- and M2(CD206) molecules, associated with pro- and anti-inflammatory activity, respectively. Here we have investigated the expression of CCR2 and CD206 in classical (CD14++CD16- , cMo), intermediate (CD14++CD16+, iMo), and non-classical monocytes (CD14+CD16++, nMo) in pregnant women at different gestational ages in comparison with nonpregnant women. The study included 14 pregnant women in the first trimester, 20 in the second trimester, 26 in the third trimester, and 29 fertile non-pregnant women. One-way analysis of variance in these groups revealed significant differences CCR2 and CD206 expression (more pronounced in classical and intermediate monocytes and stronger in relation to CD206 expression). Overall, monocytes from pregnant women had decreased CCR2- and increased CD206 expression, suggesting a shift towards an anti-inflammatory profile. These changes appeared in the first trimester (increased CD206 mean fluorescence intensity [MFI] in cMo and iMo, p < 0.05) and reached their maximum in the second trimester, manifested by significant increase in CD206 and decrease in CCR2 expression (% of cells, MFI) in all monocyte subsets. In the third trimester, CD206+ cMo decreased, as compared to the second trimester (p < 0.05), and the percentage of CCR2+ cMo and iMo increased. Of note, these changes in the first and third trimesters were combined with increased pro-inflammatory expression profile of non-classical monocytes which was restricted by the non-classical monocyte subpopulation in the first trimester, then being mediated by intermediate and non-classical monocytes in the third trimester. The data obtained suggest involvement of monocytes in regulation of the pro- and anti-inflammatory balance during pregnancy, with predominant development of the M2 profile in classical monocytes during the first and third trimesters, and in all monocyte subsets over second trimester, along with increase in the M1 proinflammatory profile of intermediate and non-classical monocytes in the first and third trimesters.

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The authors declare that there are no conflicts of interest present.