mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-ENA-2976mimmun-2976Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESУровень экспрессии генов ENTPD1, NT5E, ADORA2A, FOXP3 и RORγ в периферической крови больных язвенным колитомENTPD1, NT5E, ADORA2A, FOXP3 and RORγ gene expression in peripheral blood of patients with ulcerative colitishttps://orcid.org/0009-0006-2738-3728АторинД. А.AtorinD. A.

Аторин Даниил Алексеевич – аспирант, стажер-исследователь лаборатории генетики, ИБ КарНЦ РАН

185003, Республика Карелия, г. Петрозаводск, пр. А. Невского, 50

Тел.: 8 (8142) 57-18-79

Факс: 8 (8142) 76-98-10

Dannil A. Atorin, Postgraduate Student, Research Assistant, Laboratory of Genetics

50 A. Nevsky Ave Petrozavodsk, Republic of Karelia 185003

Phone: +7 (8142) 57-18-79

Fax: +7 (8142) 76-98-10

atorin98@mail.ruhttps://orcid.org/0000-0001-6266-3289ЖулайГ. А.ZhulaiG. A.

Жулай Г.А. – к.б.н., научный сотрудник лаборатории генетики

г. Петрозаводск, Республика Карелия

Zhulai G.A., PhD (Biology), Research Associate, Laboratory of Genetics

Petrozavodsk, Republic of Karelia

zhgali-111@yandex.ruhttps://orcid.org/0000-0001-8697-2086ТопчиеваЛ. В.TophievaL. V.

Топчиева Л.В. – к.б.н., ведущий научный сотрудник лаборатории генетики

г. Петрозаводск, Республика Карелия

Topchieva L.V., PhD (Biology), Leading Researh Associate, Laboratory of Genetics

Petrozavodsk, Republic of Karelia

topchieva67@mail.ruhttps://orcid.org/0000-0001-7620-7065КурбатоваИ. В.KurbatovaI. V.

Курбатова И.В. – к.б.н., старший научный сотрудник лаборатории генетики

г. Петрозаводск, Республика Карелия

Kurbatova I.V., PhD (Biology), Senior Research Associate, Laboratory of Genetics

Petrozavodsk, Republic of Karelia

irina7m@yandex.ruhttps://orcid.org/0000-0003-2613-5694ДудановаО. П.DudanovaO. P.

Дуданова О.П. – д.м.н., профессор, заведующая кафедрой пропедевтики внутренних болезней и гигиены Медицинского института

г. Петрозаводск, Республика Карелия

Dudanova O.P., PhD, MD (Medicine), Professor, Head, Department of Propaedeutics of Internal Diseases and Hygiene

Petrozavodsk, Republic of Karelia

odudanova@gmail.comИнститут биологии – обособленное подразделение ФГБУН «Федеральный исследовательский центр “Карельский научный центр Российской академии наук”»РоссияInstitute of Biology, Karelian Research Centre, Russian Academy of SciencesRussian FederationФГБОУ ВО «Петрозаводский государственный университет»РоссияPetrozavodsk State UniversityRussian Federation202508012025271197206Copyright © Аторин Д.А., Жулай Г.А., Топчиева Л.В., Курбатова И.В., Дуданова О.П., 20252025Аторин Д.А., Жулай Г.А., Топчиева Л.В., Курбатова И.В., Дуданова О.П.Atorin D.A., Zhulai G.A., Tophieva L.V., Kurbatova I.V., Dudanova O.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2976

Развитие язвенного колита (ЯК) сопровождается активацией пуринэргического сигнального пути и повышением уровня внеклеточного аденозина. Аденозин участвует в регуляции баланса провоспалительных Т-хелперов типа 17 (Th17) и иммуносупрессорных регуляторных Т-клеток (Treg), нарушение которого, как считается, является одним из основных иммунных факторов данного заболевания. Тем не менее вопрос о том, как изменяется экспрессия генов, кодирующих транскрипционные факторы Treg-клеток и Th17 (FOXP3 и RORγ соответственно), и генов, кодирующих участников CD39/CD73/A2AR сигнального пути (ENTPD1, NT5E, ADORA2A), в периферической крови больных ЯК малоизучен. Цель исследования – изучить уровень экспрессии генов ENTPD1, NT5E, ADORA2A, FOXP3 и RORγ при язвенном колите. Обследован 41 человек, из которых 23 пациента с диагнозом «ЯК» (18 пациентов, находящихся на базисной терапии производными 5-АСК (группа ЯК1) и 5 пациентов, принимающих преднизолон (группа (ЯК2)), 18 условно здоровых людей. Тотальную РНК выделяли из лейкоцитов периферической крови (ЛПК). Уровень транскриптов генов изучали методом ПЦР в режиме реального времени. Содержание мРНК гена ENTPD1 у больных ЯК, находящихся на базисной терапии производными 5-АСК, было выше, чем у здоровых людей (p = 0,0045). Уровень транскриптов гена NT5E и ADORA2Aв ЛПК пациентов группы ЯК1 оказался выше, чем у пациентов из группы ЯК2 (p = 0,0486 и p = 0,0289 соответственно) и здоровых индивидов (p = 0,0007 и p < 0,001 соответственно). У группы пациентов ЯК1 содержание мРНК гена FOXP3 в ЛПК было выше, чем у условно здоровых людей (p = 0,0093). Уровень экспрессии гена RORγ в ЛПК пациентов из групп ЯК1 и ЯК2 был выше, чем у здоровых индивидов (p = 0,0005). В ЛПК больных ЯК, находящихся на базисной терапии, наблюдалось повышение уровня экспрессии генов FOXP3 и RORγ, представляющих собой транскрипционные факторы Treg- и Th17-клеток соответственно, тогда как уровень экспрессии этих генов у больных ЯК на преднизолоне не отличался от контроля. В контрольной группе и группе ЯК1 выявлены корреляционные связи между уровнем экспрессии некоторых из исследуемых генов.

Development of ulcerative colitis (UC) is accompanied by activation of the purinergic signaling pathway and an increased level of extracellular adenosine. Adenosine is involved in regulating the balance of pro-inflammatory T-helper type 17 (Th17) cells and immunosuppressive regulatory T-cells (Treg), Their disturbance is believed to be one of the main immune factors causing this disease. However, expression of genes encoding Treg cell and Th17 transcription factors (FOXP3 and RORγ, respectively) and genes encoding members of the CD39/CD73/A2AR signaling pathway (ENTPD1, NT5E, ADORA2A) in peripheral blood has not been studied enough. The purpose of our study was to evaluate the expression levels of ENTPD1, NT5E, ADORA2A, FOXP3 and RORγ genes in ulcerative colitis (UC). Thirty-eight patients were examined including 20 patients diagnosed with UC (15 patients on a basic therapy with 5-ASA derivatives, UC1 group); 5 patients treated with Prednisone (group UC2), and 18 apparently healthy people. Total RNA was isolated from peripheral blood leukocytes (PBLCs). The levels of gene transcripts were studied by real-time PCR technique. The ENTPD1 gene mRNA content in UC patients on a basic therapy with 5-ASA derivatives was higher than in healthy people (p = 0.0045). The levels of NT5E and ADORA2A transcripts in the PBLCs of patients in the UC1 group were higher than those of patients in the UC2 group (p = 0.0486 and p = 0.0289, respectively) and healthy individuals (p = 0.0007 and p < 0.001, respectively). The mRNA content of FOXP3 gene in PBLCs of the UC1 group of patients was higher than in conditionally healthy individuals (p = 0.0093). The level of RORγ gene expression in PBLCs of the patients from UC1 and UC2 groups was higher than in healthy individuals (p = 0.0005). Increased levels of FOXP3 and RORγ gene expression (the transcription factors of Treg and Th17 cells, respectively), were observed in PBLCs of UC patients on baseline therapy, whereas expression levels of these genes in prednisolone-treated UC patients did not differ from controls. Correlations between the expression levels of some genes under study were revealed in control persons and in the UC1 group.

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