Metformin Reverses Hashimoto’s Thyroiditis by Regulating Key Immune Events

Abstract

BackgroundHashimoto’s thyroiditis (HT) is a common autoimmune disease characterized by high levels of thyroid peroxidase antibody (TPOAb) and thyroid globulin antibody (TgAb) as well as infiltration of lymphocytes in thyroid. In recent years, metformin has been proven to be effective in a variety of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis.MethodsThis study systematically explored the therapeutic effect of metformin on HT and its underlying mechanism by comprehensively utilizing methods including animal model, in vitro cell culture and differentiation, mRNA sequencing and 16S rRNA sequencing.FindingsWe found that metformin indeed had a therapeutic effect on mice with HT mainly by reducing TgAb and lymphocyte infiltration in thyroid tissue. In addition, metformin also significantly suppressed the number and function of Th17 cells and M1 macrophages polarization in HT mice. Furthermore, metformin can inhibit the differentiation and function of Th17 in vitro. The results of mRNA sequencing of thyroid tissue illustrated that the therapeutic effect of metformin on HT was mainly achieved by regulating immune pathways. 16S RNA sequencing of the intestinal flora found that the intestinal flora of HT mice differs significantly from that of the normal mice and also were altered by metformin treatment.InterpretationThese experiments provided a preliminary theoretical basis for the clinical application of metformin in the treatment of HT.

High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1

“…Besides, we also performed GSEA analysis of macrophage polarization in mouse thyroid tissue. mRNA-seq data were obtained from our previous study ( 34 ), including normal controls (n=3) and thyroiditis model group (n=5). GSEA results showed that M1 polarization characteristic gene set was significantly enriched in the thyroiditis group (ES=0.63, P<0.001, FDR q<0.001), while M2 was not (ES=0.38, P<0.001, FDR q<0.001) ( Figure 5C ).…”

“…In this study, a mouse thyroiditis model was constructed by high iodine water feeding and thyroglobulin immuno-injection, which was described in our previous study in detail ( 34 ). Female 6–8 weeks old C57BL/6 mice from Shanghai Model Organisms Center were kept at the SPF level and free to eat and drink.…”

A Comparative Study of Different Protocols for Isolation of Murine Neutrophils from Bone Marrow and Spleen

“…Optimization of the INS protocol for splenic neutrophil isolation could be applied to obtain untouched splenic neutrophils; however, it could be rather expensive because of the complex cocktail of antibodies that should be added to the splenocyte suspension along with the EasySep antibody cocktail [24]. Taking into account the low content of neutrophils in the spleen of healthy mice [24][25][26] and obtained data on purity/viability of cells (Table 2) the IPS protocol is recommended for splenic neutrophil isolation.…”

A Chinese Patent Medicine JiaYanKangTai Alleviates Inflammatory Lesions of Experimental Autoimmune Thyroiditis by Regulating Interleukin-17 Signaling

“…Morphological changes of thyroid were observed by an experienced technician using a BX53F optical microscope (Olympus, Tokyo, Japan) at 200× magnification. The percentage of lymphocytic infiltration area was analyzed using Image-Pro Plus 6.0 software (Media Cybernetics, Silver Spring, MD, USA) (16,17).…”