Depletion of Regulatory T Cells in Visceral Adipose Tissues Contributes to Insulin Resistance in Hashimoto's Thyroiditis.

Min Yang,Chenxi Zhang,Qin Tao,Jun Liu,Yueyue Wu,Li Su

doi:10.3389/fphys.2018.00136

Min Yang, Chenxi Zhang + Show 4 more

Open Access

https://doi.org/10.3389/fphys.2018.00136

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Abstract

Hashimoto's Thyroiditis (HT) is a common organ-specific autoimmune disorder associated with a high incidence, and insulin resistance is highly related to autoimmune. Here, we examined the insulin sensitivity in HT patients and found decreased insulin sensitivity occurred in HT patients. To explore the relationship between impaired insulin sensitivity and immune status, we established HT model mice which showed similar pathological features and immune features to HT patients. In HT model mice, reinfusion of regulatory T cells (Tregs) from peripheral blood of normal mice could improve insulin sensitivity and decrease the inflammation. Anti-CD25 antibodies blocked beneficial effects from reinfusion of Tregs, but delayed administration of anti-CD25 antibodies could not abolished the effect from Tregs. Delayed administration of anti-CD25 antibodies abolished exogenous Tregs in peripheral blood, but there were increased exogenous Tregs located to visceral adipose tissues (VATs) which modulated the expression of cytokines in VATs. These findings suggest that insulin resistance exists in HT patients and it associates with the decreased Tregs and increased inflammation in the VATs.

Highlights

Hashimoto’s Thyroiditis (HT), a common organ-specific autoimmune disorder, presents the infiltration of the thyroid gland by inflammatory cells and the production of autoantibodies to thyroid-specific antigens (Ajjan and Weetman, 2015)
Hypothyroidism is thought the major reason that links HT to insulin resistance (Fernandez-Real et al, 2006), the abnormal immune in HT might relate to insulin resistance directly
We provided that decreased level of CD25+Foxp3+ Tregs in HT model mice related to increased early phase and total insulin secretion, and the reinfusion of CD25+Foxp3+ Tregs separated from peripheral blood of normal mice restored the insulin sensitivity in HT model mice

Summary

Introduction

Hashimoto’s Thyroiditis (HT), a common organ-specific autoimmune disorder, presents the infiltration of the thyroid gland by inflammatory cells and the production of autoantibodies to thyroid-specific antigens (Ajjan and Weetman, 2015). HT is associated with the destruction of thyroid cells, and hypothyroidism is the main clinical manifestation (Isgüven et al, 2016). Hypothyroidism is associated with the susceptibility of insulin resistance and metabolic syndromes (Fernandez-Real et al, 2006; Roos et al, 2007; Jornayvaz et al, 2012). HT should be connected to insulin resistance directly. The reason that induces insulin resistance in HT patients is not clear.

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