gastro-jРоссийский журнал гастроэнтерологии, гепатологии, колопроктологииRussian Journal of Gastroenterology, Hepatology, Coloproctology1382-43762658-6673«Gastro» LLC10.22416/1382-4376-2024-34-4-86-93gastro-j-976Research ArticleНАЦИОНАЛЬНАЯ ШКОЛА ГАСТРОЭНТЕРОЛОГИИ, ГЕПАТОЛОГИИNATIONAL COLLEGE OF GASTROENTEROLOGY, HEPATOLOGYРоль макрофагов в патогенезе целиакииThe Role of Macrophages in the Pathogenesis of Celiac Diseasehttps://orcid.org/0000-0001-7308-7280ХавкинА. И.KhavkinA. I.

Анатолий Ильич Хавкин, доктор медицинских наук, профессор, заведующий кафедрой, профессор кафедры

кафедра гастроэнтерологии и диетологии им. А.В. Мазурина; Медицинский институт; кафедра педиатрии с курсом детских хирургических болезней

115093; ул. Большая Серпуховская, 62; Москва; Белгород

Anatoly I. Khavkin, Dr. Sci. (Med.), Professor, Head of the Department, Professor of the Department

Department of Gastroenterology and Dietetics named after A.V. Mazurin; Department of Pediatrics with a Course in Pediatric Surgical Diseases

115093;  Bolshaya Serpukhovskaya str., 62; Moscow; Belgorod

khavkin@nikid.ruhttps://orcid.org/0000-0002-3043-8674ЛошковаЕ. В.LoshkovaE. V.

Елена Владимировна Лошкова, кандидат медицинских наук, ведущий научный сотрудник, заместитель главного врача по клинико-экспертнойработе, ведущий научный сотрудник

научно-организационный отдел; Институт высшего и дополнительного профессионального образования; научно-клинический отдел муковисцидоза

141009; ул. Коминтерна, 24А, стр. 1; Москва

Elena V. Loshkova, Cand. Sci. (Med.), Associate Professor, Leading Researcher, Deputy Chief Physician for Clinical and Expert Work, Leading Researcher 

Scientific and Organizational Department; Institute of Higher and Continuing Professional Education; Scientific and Clinical Department of Cystic Fibrosis

141009; Kominterna str., 23A, build. 1; Moscow

loshkova@rambler.ruhttps://orcid.org/0000-0001-6395-0407КондратьеваЕ. И.KondratievaE. I.

Елена Ивановна Кондратьева, доктор медицинских наук, профессор, заместитель директора, руководитель отдела, заведующая кафедрой

научно-клинический отдел муковисцидоза; Институт высшего и дополнительного профессионального образования; кафедра генетики болезней дыхательной системы

115522; ул. Москворечье, 1; Москва; Томск

Elena I. Kondratieva, Dr. Sci. Med., Professor, Deputy Director, Head of theDepartment

Scientific and Clinical Department of Cystic Fibrosis; Institute of Higher and Continuing Professional Education; Department of Genetic and Respiratory Diseases

115522; Moskvorechye str. 1; Moscow; Tomsk

https://orcid.org/0000-0002-0364-6785ШаповаловаН. С.ShapovalovaN. S.

Наталья Сергеевна Шаповалова, кандидат медицинских наук, ведущий научный сотрудник

отдел педиатрии

141009; ул. Коминтерна, 24А, стр. 1; Москва; Мытищи

Natalia S. Shapovalova, Cand. Sci. (Med.), Leading Researcher

Department of Pediatrics

141009; Kominterna str., 23A, build. 1; Moscow; Mytishchi

natasunday@mail.ruhttps://orcid.org/0000-0002-8581-7049ГришкевичИ. Р.GrishkevichI. R.

Иван Романович Гришкевич, студент

педиатрический факультет

634050; Московский тракт, 2; Томск

Ivan R. Grishkevich, Student

Faculty of Pediatrics

634050; Moskovsky Trakt, 2; Tomsk

vanya0902w@icloud.comhttps://orcid.org/0000-0002-0747-5952ДорошенкоИ. В.DoroshenkoI. V.

Иван Владимирович Дорошенко, студент

педиатрический факультет

634050; Московский тракт, 2; Томск

Ivan V. Doroshenko, Student

Faculty of Pediatrics

634050; Moskovsky Trakt, 2; Tomsk

vanyadoro2016@gmail.comhttps://orcid.org/0000-0001-5792-2012ЯнкинаГ. Н.YankinaG. N.

Галина Николаевна Янкина, доктор медицинских наук, профессор

кафедра госпитальной педиатрии

634050; Московский тракт, 2; Томск

Galina N. Yankina, Dr. Sci. (Med.), Professor

Department of Hospital Pediatrics

634050; Moskovsky Trakt, 2; Tomsk

gal.happy@mail.ruГБУЗ Московской области «Научно-исследовательский клинический институт детства Министерства здравоохранения Московской области»; ФГАОУ ВО «Белгородский государственный национальный исследовательский университет»РоссияResearch Clinical Institute of Childhood of the Ministry of Healthcare of the Moscow Region; Belgorod State National Research UniversityRussian FederationГБУЗ Московской области «Научно-исследовательский клинический институт детства Министерства здравоохранения Московской области»; ФГБНУ «Медико-генетический научный центр им. академика Н.П. Бочкова»РоссияResearch Clinical Institute of Childhood of the Ministry of Healthcare of the Moscow Region; Research Center for Medical GeneticsRussian FederationГБУЗ Московской области «Научно-исследовательский клинический институт детства Министерства здравоохранения Московской области»; ФГБОУ ВО «Сибирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияResearch Clinical Institute of Childhood of the Ministry of Healthcare of the Moscow Region; Siberian State Medical UniversityRussian FederationГБУЗ Московской области «Научно-исследовательский клинический институт детства Министерства здравоохранения Московской области»РоссияResearch Clinical Institute of Childhood of the Ministry of Healthcare of the Moscow RegionRussian FederationФГБОУ ВО «Сибирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияSiberian State Medical UniversityRussian Federation2024071020243448693Copyright © Хавкин А.И., Лошкова Е.В., Кондратьева Е.И., Шаповалова Н.С., Гришкевич И.Р., Дорошенко И.В., Янкина Г.Н., 20242024Хавкин А.И., Лошкова Е.В., Кондратьева Е.И., Шаповалова Н.С., Гришкевич И.Р., Дорошенко И.В., Янкина Г.Н.Khavkin A.I., Loshkova E.V., Kondratieva E.I., Shapovalova N.S., Grishkevich I.R., Doroshenko I.V., Yankina G.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gastro-j.ru/jour/article/view/976   Цель

   Цель: представить данные об участии макрофагов в патогенезе целиакии и разработке возможных методов лечения этого заболевания, направленных на изменение функции макрофагов.

   Основные положения

   Основные положения. Целиакия — это аутоиммунное заболевание с характерным серологическим (антитела к тканевой трансглутаминазе, эндомизию, деамидированным пептидам глиадина) и гистологическим профилем (воспалительная инфильтрация эпителия ворсинок лимфоцитами и их атрофия, гиперплазия крипт), вызванным употреблением глютена у генетически предрасположенных лиц. Макрофаги как ключевые клетки, обеспечивающие связь врожденного и адаптивного иммунитета, имеют существенное значение в патогенезе целиакии. Пептиды глиадина стимулируют активацию макрофагов по провоспалительному фенотипу с продукцией цитокинов, что служит причиной иммунного ответа Т-хелперов 1 и Т-хелперов 17. Результатом этих процессов служит развитие воспалительной реакции и повреждение слизистой оболочки кишечника за счет продукции макрофагами матриксных металлопротеиназ и активных форм кислорода. Терапевтическая тактика целиакии на сегодняшний день включает безглютеновую диету, которая не так проста в соблюдении. Интерес представляет изучение возможности применения при целиакии полифенолов, которые способны осаждать глиадины и ингибировать поляризацию макрофагов в сторону провоспалительного фенотипа, одновременно стимулируя увеличение популяции макрофагов противовоспалительного фенотипа, ассоциированного с уменьшением тканевого повреждения.

   Заключение

   Заключение. Нарушение функции/дифференцировки макрофагов приводит либо к неадекватной, чрезмерной активации иммунитета, либо к неспособности индуцировать эффективные защитные иммунные реакции против патогенов, в результате чего возможно развитие заболеваний желудочно-кишечного тракта. Изучение участия макрофагов на разных этапах прогрессирования целиакии является важным для разработки новых методов лечения данного заболевания.

Aim

Aim: to present data on the involvement of macrophages in the pathogenesis of celiac disease and the development of possible treatment methods for this disease aimed at changing the function of macrophages.

Key points

Key points. Celiac disease is an autoimmune disease with a characteristic serological (antibodies to tissue transglutaminase, endomysium, deamidated gliadin peptides) and histological profile (inflammatory infiltration of the villous epithelium by lymphocytes and their atrophy, crypt hyperplasia) caused by gluten consumption in genetically predisposed individuals. Macrophages, as key cells that provide a link between innate and adaptive immunity, are of significant importance in the pathogenesis of celiac disease. Gliadin peptides stimulate the activation of macrophages according to the proinflammatory phenotype with the production of cytokines, which causes the immune response of T-helpers 1 and T-helpers 17. The result of these processes is the development of an inflammatory reaction and damage to the intestinal mucosa due to the production of matrix metalloproteinases and reactive oxygen species by macrophages. Therapeutic tactics for celiac disease today include a gluten-free diet, which is not so easy to follow. Of interest is the study of the possibility of using polyphenols in celiac disease, which are capable of precipitating gliadins and inhibiting the polarization of macrophages towards a proinflammatory phenotype, while simultaneously stimulating an increase in the population of macrophages of an anti-inflammatory phenotype associated with a decrease in tissue damage.

Conclusion

Conclusion. Impaired macrophage function/differentiation results in either inadequate, excessive immune activation or failure to mount effective protective immune responses against pathogens, which may result in the development of gastrointestinal diseases. Studying the involvement of macrophages at different stages of celiac disease progression is important for the development of new treatments for this disease.

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