Genetics, Epigenetics, Cellular Immunology, and Gut Microbiota: Emerging Links With Graves’ Disease

Abstract

Graves’ disease (GD) is a well-known organ-specific autoimmune disease characterized by hyperthyroidism, goiter, and exophthalmos. The incidence of GD is approximately 2.0–3.0% in China and 0.5–2.0% in Western countries. Due to the complex pathogenesis and etiology of GD, current treatment methods have great side effects that seriously endanger human health. Therefore, it is particularly important to understand the pathogenesis of GD. Various studies have shown that genetics, epigenetics, cellular immunology, and gut microbiota are all involved in the development of GD. Genetically, CD25 gene and VDR gene polymorphisms are involved in the development of GD by increasing the ratio of Th17/Treg cells. Epigenetically, miR-23a-3p and lncRNA-MEG3 lead to Th17/Treg imbalance and participate in the progression of GD. Moreover, commensal microbe deletion can disrupt Th17/Treg balance and participate in the occurrence of GD. The imbalance of Th17/Treg cells induced by genetics, epigenetics, and gut microbiota plays a vital role in the pathogenesis of GD. Therefore, this article reviews the role of genetics, epigenetics, cellular immunology, and gut microbiota in the pathogenic mechanism of GD. This may lead to the development of novel therapeutic strategies and providing promising therapeutic targets.

Graves Disease and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization

“…IGFBP4 methylation is increased in CD patients compared to UC patients, and thyroid hormone levels may be associated with the IGF-1/IGFBP system ( 46 , 47 ). Recently, published studies have shown that the imbalance of T-helper 17/regulator T cells induced by epigenetics also plays a vital role in CD ( 48 , 49 ).…”

Celastrol alleviates murine lupus nephritis via inducting CD4+Foxp3+ regulatory T cells

“…In addition, it significantly suppresses serum levels of anti-cyclic citrullinated protein/peptide (aCCP) antibodies as well as MMP-9 activity [10]. Proper immune balance between T helper cell 17 (Th17) and Tregs is necessary to avoid autoimmune-related immunopathology [39][40][41]. CLT has been revealed to regulate Th17/Treg ratio in the joints of rats with adjuvant arthritis [21].…”

Molecular Mechanisms in Autoimmune Thyroid Disease

“…Among the epigenetic factors associated with AITD, the skewed X-chromosome inactivation (XCI) SNPs of the genes involved in DNA methylation, the DNA methyltransferases (DNMTs) genes, or the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes stand out. Other SNPs have also been implicated, such as the immunoregulatory factors ADRB2 (hypermethylated), ICAM1 (hypomethylated), and B3GNT2 (hypermethylated), as well as histone modifications and the impaired expression of noncoding RNAs, among other factors [ 215 , 216 ].…”