vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ20.672vavilov-2820Research ArticleРЕПРОДУКТИВНЫЕ ТЕХНОЛОГИИPHYSIOLOGICAL GENETICSСубпопуляционный состав периферических иммунокомпетентных клеток и содержание цитокинов в структурах мозга у мутантных мышей линии Disk1-Q31LThe composition of peripheral immunocompetent cell subpopulations and cytokine content in the brain structures of mutant Disc1-Q31L miceГеворгянМ. М.GevorgyanM. M.

Новосибирск

Novosibirsk

ЖанаеваС. Я.ZhanaevaS. Ya.

Новосибирск

Novosibirsk

АльперинаЕ. Л.AlperinaE. L.

Новосибирск

Novosibirsk

ЛипинаТ. В.LipinaT. V.

Новосибирск

Novosibirsk

ИдоваГ. В.IdovaG. V.

Новосибирск

Novosibirsk

galina-idova@mail.ruНаучно-исследовательский институт физиологии и фундаментальной медициныРоссияScientific Research Institute of Physiology and Basic MedicineRussian Federation202005122020247770776Copyright © Геворгян М.М., Жанаева С.Я., Альперина Е.Л., Липина Т.В., Идова Г.В., 20202020Геворгян М.М., Жанаева С.Я., Альперина Е.Л., Липина Т.В., Идова Г.В.Gevorgyan M.M., Zhanaeva S.Y., Alperina E.L., Lipina T.V., Idova G.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/2820

Нарушения в гене DISC1 (disrupted in sсhizophrenia 1) ассоциированы с дисфункциями мозга, характерными для ряда психических заболеваний (шизофрения, депрессия, биполярное расстройство и др.). В данной работе впервые изучены иммунологические параметры у мышей линии Disc1-Q31L с точечной мутацией во втором экзоне гена DISC1 (замена глутамина на лейцин в 31-м положении) по сравнению с мышами линии C57BL/6NCrl (дикий тип). Методом проточной цитофлуориметрии показано, что по сравнению с мышами дикого типа у интактных Disc1-Q31L мышей в периферической крови увеличено процентное содержание CD3+ Т-лимфоцитов, CD3+CD4+ Т-хелперов и CD3+CD4+CD25+ Т-регуляторных клеток при снижении CD3+CD8+ Т-цитотоксических/супрессорных клеток. С помощью мультиплексного анализа выявлены различия в содержании цитокинов в структурах мозга Disc1-Q31L мышей по сравнению с мышами дикого типа. Содержание провоспалительных цитокинов повышалось во фронтальной коре (IL-6, IL-17 и IFNγ) и стриатуме (IFNγ), а в гиппокампе и гипоталамусе, напротив, уменьшалось. При этом IL-1β снижался во всех исследованных структурах. Наряду с этим обнаружено увеличение количества противовоспалительного цитокина IL-4 во фронтальной коре и снижение IL-10 в гиппокампе. Иммунная реактивность на введение антигена эритроцитов барана, анализируемая по числу антителообразующих клеток в селезенке, на пике иммунного ответа у Disc1-Q31L мышей была выше, чем у мышей дикого типа. Таким образом, мыши линии Disc1-Q31L характеризуются изменением паттерна цитокинов в структурах мозга, усилением периферического Т-клеточного звена с повышением субпопуляций CD3+CD4+ Т-хелперов и CD3+CD4+CD25+ Т-регуляторных клеток, а также увеличением иммунной реактивности на антиген в селезенке.

The DISC1 (disrupted in sсhizophrenia 1) gene is associated with brain dysfunctions, which are involved in a variety of mental disorders, such as schizophrenia, depression and bipolar disorder. This is the first study to examine the immune parameters in Disc1-Q31L mice with a point mutation in the second exon of the DISC1 gene compared to mice of the C57BL/6NCrl strain (WT, wild type). A flow cytometry assay has shown that intact Disc1-Q31L mice differ from the WT strain by an increase in the percentage of CD3+ T cells, CD3+CD4+ Т helper cells and CD3+CD4+CD25+ T regulatory cells and a decrease in CD3+CD8+ T cytotoxic/suppressor cells in the peripheral blood. A multiplex analysis revealed differences in the content of cytokines in the brain structures of Disc1-Q31L mice compared to WT mice. The content of pro-inflammatory cytokines was increased in the frontal cortex (IL-6, IL- 17 and IFNγ) and striatum (IFNγ), and decreased in the hippocampus and hypothalamus. At the same time, the levels of IL-1β were decreased in all structures being examined. In addition, the content of anti-inflammatory cytokines IL-4 was increased in the frontal cortex, while IL-10 amount was decreased in the hippocampus. Immune response to sheep red blood cells analyzed by the number of antibody-forming cells in the spleen was higher in Disc1-Q31L mice at the peak of the reaction than in WT mice. Thus, Disc1-Q31L mice are characterized by changes in the pattern of cytokines in the brain structures, an amplification of the peripheral T-cell link with an increase in the content of the subpopulations of CD3+CD4+ T helpers and CD3+CD4+CD25+ T regulatory cells, as well as elevated immune reactivity to antigen in the spleen.

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