Molecular Epigenetic Modulation of Immune Tolerance in Graves' Disease: The Role of Short-Chain Fatty Acids in the Regulation of TRAb Synthesis
R. M. Gabibullaev,
A. A. Udagova,
S. A. Ibragimova,
L. R. Khorava,
V. A. Prokurorova,
R. A. Azizova,
H. A. Alikhanova,
E. I. Merzhoeva,
Ya. E. Maltseva,
Ya. E. Simakova,
A. A. Pak https://doi.org/10.14341/ket12851
Abstract
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.
About the Authors
R. M. Gabibullaev
Endocrinology Research Centre
Russian Federation
Russian Federation
Ramazan M. Gabibullaev, MD, resident
11 Dm.Ulyanova street, 117292, Moscow
A. A. Udagova
Endocrinology Research Centre
Russian Federation
Russian Federation
Aishat A. Udagova, MD, resident
Moscow
S. A. Ibragimova
Endocrinology Research Centre
Russian Federation
Russian Federation
Saida A. Ibragimova, MD
Moscow
L. R. Khorava
Pirogov Russian National Research Medical University (Pirogov University), Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Lika R. Khorava, student
Moscow
V. A. Prokurorova
Pirogov Russian National Research Medical University (Pirogov University), Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Viktoria A. Prokurorova, student
Moscow
R. A. Azizova
Pirogov Russian National Research Medical University (Pirogov University), Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Raisat A. Azizova, student
Moscow
H. A. Alikhanova
Pirogov Russian National Research Medical University (Pirogov University), Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Hadizhat A. Alikhanova, student
Moscow
E. I. Merzhoeva
Sechenov First Moscow State Medical University
Russian Federation
Russian Federation
Eset I. Merzhoeva, student
Moscow
Ya. E. Maltseva
Sechenov First Moscow State Medical University
Russian Federation
Russian Federation
Yana E. Maltseva, student
Moscow
Ya. E. Simakova
Russian University of Medicine
Russian Federation
Russian Federation
Yana E Simakova, student
Moscow
A. A. Pak
Russian University of Medicine
Russian Federation
Russian Federation
Anastasia A. Pak, student
Moscow
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Supplementary files
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1. Figure 1. Pathogenetic scheme of interaction between intestinal microbiota and the immune system in Graves' disease. Notes: ЛПС - lipopolysaccharide; АПК - antigen-presenting cell; Th17 - T-helper cells type 17; Tregs - regulatory T-cells; АТ-рТТГ - antibodies to the thyroid-stimulating hormone receptor; ТТГ - thyroid-stimulating hormone; T3 - triiodothyronine; T4 - thyroxine. | |
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2. Figure 2. Molecular mechanism of epigenetic modulation of regulatory T cell (Treg) differentiation under the influence of SCFAs. | |
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| Type | Исследовательские инструменты | |
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For citations:
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 Ya.E., Simakova Ya.E., Pak A.A. Molecular Epigenetic Modulation of Immune Tolerance in Graves' Disease: The Role of Short-Chain Fatty Acids in the Regulation of TRAb Synthesis. Clinical and experimental thyroidology. 2025;21(3):23-31. (In Russ.) https://doi.org/10.14341/ket12851
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