ketendoКлиническая и экспериментальная тиреоидологияClinical and experimental thyroidology1995-54722310-3787Endocrinology Research Centre10.14341/ket12851ketendo-12851Research ArticleНаучный обзорReviewЭпигенетическая модуляция иммунной толерантности при болезни Грейвса: роль короткоцепочечных жирных кислот в регуляции синтеза АТ-рТТГMolecular Epigenetic Modulation of Immune Tolerance in Graves' Disease: The Role of Short-Chain Fatty Acids in the Regulation of TRAb Synthesishttps://orcid.org/0009-0007-4725-8307ГабибуллаевР. М.GabibullaevR. M.

Габибуллаев Рамазан Максудович, ординатор

117292, Москва, ул. Дм. Ульянова, д. 11 

Ramazan M. Gabibullaev, MD, resident

11 Dm.Ulyanova street, 117292, Moscow

Ramazan.gab79@mail.ruhttps://orcid.org/0009-0007-2171-7106УдаговаА. А.UdagovaA. A.

Удагова Айшат Айваровна, ординатор

Москва

Aishat A. Udagova, MD, resident

Moscow

udagova79@gmail.comhttps://orcid.org/0009-0005-4780-8327ИбрагимоваС. А.IbragimovaS. A.

Ибрагимова Саида Абдурашидовна

Москва

Saida A. Ibragimova, MD

Moscow

Ibragimova.Saida@endocrincentr.ruhttps://orcid.org/0009-0000-6667-3126ХораваЛ. Р.KhoravaL. R.

Хорава Лика Ревазовна, студент

Москва

Lika R. Khorava, student

Moscow

xorava.2001@mail.ruhttps://orcid.org/0009-0009-2767-2257ПрокуророваВ. А.ProkurorovaV. A.

Прокуророва Виктория Александровна, студент

Москва

Viktoria A. Prokurorova, student

Moscow

vikaprokurorova00@mail.ruhttps://orcid.org/0009-0001-3113-0372АзизоваР. А.AzizovaR. A.

Азизова Раисат Абдуризаковна, студент 

Москва

Raisat A. Azizova, student

Moscow

rst.2016.infa@yandex.ruhttps://orcid.org/0009-0003-7402-0071АлихановаХ. А.AlikhanovaH. A.

Алиханова Хадижат Абдулхаликовна, студент

Москва

Hadizhat A. Alikhanova, student

Moscow

Hadij555@yandex.ruhttps://orcid.org/0009-0002-9101-0708МержоеваЭ. И.MerzhoevaE. I.

Мержоева Эсет Иссаевна, студент

Москва

Eset I. Merzhoeva, student

Moscow

merzhoyeva.asya@mail.ruhttps://orcid.org/0009-0009-9164-842XМальцеваЯ. Е.MaltsevaYa. E.

Мальцева Яна Евгеньевна, студент

Москва

Yana E. Maltseva, student

Moscow

yana33973@gmail.comhttps://orcid.org/0009-0004-9989-0812СимаковаЯ. Э.SimakovaYa. E.

Симакова Яна Эдуардовна, студент

Москва

Yana E Simakova, student

Moscow

yana.simakova.2018@bk.ruhttps://orcid.org/0009-0005-2276-1542ПакА. А.PakA. A.

Пак Анастасия Алексеевна, студент

Москва

Anastasia A. Pak, student

Moscow

pak_nastya27@bk.ruНациональный медицинский исследовательский центр эндокринологии им. академика И.И. ДедоваРоссияEndocrinology Research CentreRussian FederationРоссийский национальный исследовательский медицинский университет им. Н.И. ПироговаРоссияPirogov Russian National Research Medical University (Pirogov University), Ministry of Health of the Russian FederationRussian FederationПервый Московский государственный медицинский университет им. И.М. СеченоваРоссияSechenov First Moscow State Medical UniversityRussian FederationРоссийский университет медициныРоссияRussian University of MedicineRussian Federation2025160620262132331Copyright © Габибуллаев Р.М., Удагова А.А., Ибрагимова С.А., Хорава Л.Р., Прокуророва В.А., Азизова Р.А., Алиханова Х.А., Мержоева Э.И., Мальцева Я.Е., Симакова Я.Э., Пак А.А., 20262026Габибуллаев Р.М., Удагова А.А., Ибрагимова С.А., Хорава Л.Р., Прокуророва В.А., Азизова Р.А., Алиханова Х.А., Мержоева Э.И., Мальцева Я.Е., Симакова Я.Э., Пак А.А.Gabibullaev R.M., Udagova A.A., Ibragimova S.A., Khorava L.R., Prokurorova V.A., Azizova R.A., Alikhanova H.A., Merzhoeva E.I., Maltseva Y.E., Simakova Y.E., Pak A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.cet-endojournals.ru/jour/article/view/12851

Болезнь Грейвса представляет собой системный аутоиммунный процесс, в основе которого лежит стойкое нарушение иммунной толерантности и персистенция антител к рецептору тиреотропного гормона (АТ-рТТГ), сохраняющаяся даже после радикального удаления щитовидной железы (ЩЖ). В представленном обзоре рассматривается роль оси «кишечник — щитовидная железа» в качестве ключевого регулятора системного иммунного гомеостаза. Особое внимание уделено короткоцепочечным жирным кислотам (КЦЖК) — продуктам микробного метаболизма, которые выступают в качестве мощных эпигенетических модуляторов. Детально описаны механизмы ингибирования гистондеацетилаз (HDAC) бутиратом и пропионатом, что способствует стабилизации экспрессии гена Foxp3 в регуляторных Т-клетках и подавлению факторов дифференцировки В-лимфоцитов (AID, Blimp-1). Проанализирована взаимосвязь между кишечным дисбиозом, повышенной проницаемостью барьера и неконтролируемой продукцией аутоантител. В заключении обсуждаются перспективные стратегии таргетной терапии, включая трансплантацию фекальной микробиоты (ТФМ) и использование селективных ингибиторов HDAC, направленных на восстановление иммунного контроля при рефрактерных формах заболевания.

Graves’ disease is a systemic autoimmune process characterized by persistent breakdown of immune tolerance and continued presence of thyrotropin receptor autoantibodies (TRAb), even after radical thyroidectomy. This review examines the role of the “gut–thyroid axis” as a key regulator of systemic immune homeostasis. Particular attention is paid to short-chain fatty acids (SCFAs) — microbial metabolites that act as potent epigenetic modulators. The mechanisms of histone deacetylase (HDAC) inhibition by butyrate and propionate are described in detail, which promote stabilization of Foxp3 gene expression in regulatory T cells and suppression of B-lymphocyte differentiation factors (AID, Blimp-1). The interplay between intestinal dysbiosis, increased barrier permeability, and uncontrolled autoantibody production is analyzed. In conclusion, prospective targeted therapeutic strategies are discussed, fecal microbiota transplantation (FMT), and the use selective HDAC inhibitors aimed at restoring immune control in refractory forms of the disease.

Болезнь Грейвсакороткоцепочечные жирные кислотыэпигенетикаантитела к рецептору ТТГмикробиота кишечникаиммунная толерантностьGraves' diseaseshort-chain fatty acidsepigeneticsTSH receptor antibodiesGut microbiotaimmune toleranceРабота выполнена по инициативе авторов без привлечения финансирования.ReferencesSmith TJ, Hegedüs L. Graves’ Disease. N Engl J Med. 2016;375(16):1552-1565. doi:10.1056/NEJMra1510030.Smith TJ, Hegedüs L. Graves’ Disease. N Engl J Med. 2016;375(16):1552-1565. doi:10.1056/NEJMra1510030.Wiersinga WM, Poppe KG, Effraimidis G. Hyperthyroidism: aetiology, pathogenesis, diagnosis, management, complications, and prognosis. Lancet Diabetes Endocrinol. 2023;11(4):282-298. doi:10.1016/S2213-8587(23)00005-0.Wiersinga WM, Poppe KG, Effraimidis G. Hyperthyroidism: aetiology, pathogenesis, diagnosis, management, complications, and prognosis. Lancet Diabetes Endocrinol. 2023;11(4):282-298. doi:10.1016/S2213-8587(23)00005-0.Bahn RS, Heufelder AE. 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The authors declare that there are no conflicts of interest present.