nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2023-1S-15-21nnp-2072Research ArticleORIGINAL INVESTIGATIONSОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ И МЕТОДИКИContribution of B-lymphocytes to the production of Interleukin-17 in multiple sclerosisВклад В-лимфоцитов в продукцию интерлейкина 17 при рассеянном склерозеhttps://orcid.org/0000-0001-8876-4379СурсяковаН. В.SursyakovaN. V.

614990, Пермь, ул. Петропавловская, 26

126, Petropavlovskaya St., Perm 614990

https://orcid.org/0000-0002-2173-2724КуклинаЕ. М.KuklinaE. M.

614081, Пермь, ул. Голева, 13

213, Goleva St., Perm 614081

https://orcid.org/0000-0002-5114-0463БайдинаТ. В.BaidinaT. V.

614990, Пермь, ул. Петропавловская, 26

https://orcid.org/0000-0002-6706-5912НекрасоваИ. В.NekrasovaI. V.

614081, Пермь, ул. Голева, 13

13, Goleva St., Perm 614081

https://orcid.org/0000-0001-9199-7392ТрушниковаТ. Н.TrushnikovaT. N.

Татьяна Николаевна Трушникова

614990, Пермь, ул. Петропавловская, 26

Tat'yana Nikolaevna Trushnikova

126, Petropavlovskaya St., Perm 614990

trushnikova.t@mail.ruФГБОУ ВО «Пермский государственный медицинский университет им. акад. Е.А. Вагнера» Минздрава РоссииРоссияAcad. E.A. Vagner Perm State Medical University, Ministry of Health of RussiaRussian FederationИнститут экологии и генетики микроорганизмов Уральского отделения Российской академии наук – филиал ФГБУН «Пермский федеральный исследовательский центр Уральского отделения Российской академии наук»РоссияInstitute of Ecology and Genetics of Microorganisms of the Ural Branch of the Russian Academy of Sciences – the Branch of the Perm Federal Research Center of the Ural Branch of the Russian Academy of SciencesRussian FederationИнститут экологии и генетики микроорганизмов Уральского отделения Российской академии наук – филиал ФГБУН «Пермский федеральный исследовательский центр Уральского отделения Российской академии наук»РоссияInstitute of Ecology and Genetics of Microorganisms of the Ural Branch of the Russian Academy of Sciences – the Branch of the Perm Federal Research Center of the Ural Branch of the Russian Academy of SciencesRussian Federation202321082023150(Suppl. 1)1521Copyright © Sursyakova N.V., Kuklina E.M., Baidina T.V., Nekrasova I.V., Trushnikova T.N., 20232023Сурсякова Н.В., Куклина Е.М., Байдина Т.В., Некрасова И.В., Трушникова Т.Н.Sursyakova N.V., Kuklina E.M., Baidina T.V., Nekrasova I.V., Trushnikova T.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/2072

The study of pathogenic systems involved in multiple sclerosis (MS) is essential for the development of new therapies.Objective: to determine the contribution of B-lymphocytes to the production of IL-17 in MS with an assessment of the ability of B-cells to induce the differentiation of Th17 and the own production of IL-17 by B-lymphocytes in this pathology.Material and methods. A total of 81 subjects were examined, 68 of whom were patients diagnosed with MS, 13 were healthy individuals. The concentrations of IL-17A, IL-10, BAFF and total IgG were analyzed in blood serum by ELISA. The additional study included 13 MS patients and 11 healthy donors. Mononuclear cells were isolated from the blood, from which B-lymphocytes and CD4+T-lymphocytes were obtained. B-lymphocytes were incubated with tetanus toxoid or with myelin-oligodendrocyte glycoprotein (MOG), after which they were washed from unbounded antigen and cultured together with autologous CD4+T-lymphocytes or with peripheral blood mononuclear cells, then the content of Th17 cells in the sample was evaluated. Flow cytometry ex vivo assessed the expression of RORγt by B-lymphocytes and CD4+T-lymphocytes. The level of IL-17 in blood serum and cell culture supernatants was determined by ELISA.Results. High IL-17 serum levels in MS patients are associated with elevated BAFF concentrations, and in patients with high IgG levels, IL-17 concentrations were also twice as high. A statistically significant higher level of IL-17-positive B-lymphocytes was detected in MS.Conclusion. B-lymphocytes may contribute to the production of IL-17 in MS in two ways – by inducing the differentiation of T-lymphocytes producing this cytokine and by their own synthesis of IL-17.

Изучение патогенетических систем, участвующих в рассеянном склерозе (РС), необходимо для разработки новых подходов к терапии.Цель исследования – определить вклад В-лимфоцитов в продукцию интерлейкина 17 (ИЛ17) при РС с оценкой способности В-клеток индуцировать дифференцировку Th17, собственной продукции ИЛ17 В-лимфоцитами при данной патологии.Материал и методы. Обследованы 81 человек, из них 68 – пациенты с диагнозом РС, 13 – здоровые доноры. В сыворотке крови исследованы концентрации ИЛ17A, ИЛ10, факторов, ассоциированных с дифференцировкой (BAFF), и общего IgG методом иммуноферментного анализа. В дополнительном исследовании участвовали 13 пациентов с РС и 11 здоровых доноров. Из крови выделяли мононуклеарные клетки, из которых получали В-лимфоциты и CD4+Т-лимфоциты. В-лимфоциты инкубировали с столбнячным анатоксином (ТТ) или с миелин-олигодендроцитарным гликопротеином, после чего отмывали от несвязавшегося антигена и культивировали совместно с аутологичными CD4+Т-лимфоцитами или с мононуклеарными клетками периферической крови, затем оценивали содержание в пробе клеток Th17. С использованием проточной цитометрии ex vivo оценивали экспрессию RORγt В-лимфоцитами и CD4+Т-лимфоцитами. Уровень ИЛ17 в сыворотке крови и в супернатантах клеточных культур определяли методом иммуноферментного анализа.Результаты. Высокий уровень ИЛ17 в сыворотке пациентов с РС ассоциирован с повышенной концентрацией BAFF, у пациентов с высоким уровнем IgG концентрация ИЛ17 также была вдвое выше. Показано статистически значимо более высокое содержание ИЛ17-позитивных В-лимфоцитов при РС.Заключение. В-лимфоциты могут вносить вклад в продукцию ИЛ17 при РС двумя путями – за счет индукции дифференцировки Т-лимфоцитов, продуцирующих данный цитокин, и за счет собственного синтеза ИЛ17.

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