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Regenerative potentials of the murine thyroid in experimental autoimmune thyroiditis: role of CD24.

ABSTRACT: Hashimoto thyroiditis can be partially reproduced in mice by immunization with thyroglobulin or, more recently, thyroperoxidase. This experimental autoimmune thyroiditis (EAT) model has been extensively characterized during early disease phases (up to d 35 after immunization). By extending the analysis of EAT to 100 d after immunization, we noted a remarkable regenerative capacity of the thyroid and the expression of Oct-4, suggesting in vivo the existence of adult thyroid stem cells. After an almost complete destruction of the follicular architecture, occurring between d 21 and 28, the thyroid was capable of restoring its follicles and reducing the mononuclear infiltration, so that by d 100 after immunization, it regained its normal morphology and function. During this regeneration process, thyrocytes expressed high levels of CD24. We therefore assessed the role of CD24 in thyroid regeneration by inducing EAT in mice lacking CD24. Regeneration was faster in the absence of CD24, likely a consequence of the effect of CD24 on the infiltrating lymphocytes. The study suggests that the EAT model can also be used as a tool to investigate adult thyroid stem cells.

SUBMITTER: Chen CY

PROVIDER: S-EPMC2630910 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Inflammation is an important contributor to autoimmune thyroiditis. Yanghe decoction (YH) is a traditional Chinese herbal formulation which has various anti-inflammatory effects. It has been used for the treatment of autoimmune diseases such as ankylosing spondylitis In this study we aimed to investigate the effects of YH on autoimmune thyroiditis in a rat model and elucidate the underlying mechanisms. The experimental autoimmune thyroiditis (EAT) model was established by thyroglobulin (pTG) injections and excessive iodine intake. Thyroid lesions were observed using hematoxylin and eosin (H and E) staining and serum TgAb, TPOAb, TSH, T3, and T4 levels were measured by enzyme-linked immunosorbent assay IL-35 levels were evaluated using real-time polymerase chain reaction (RT-PCR) and Th17/Treg balance in peripheral blood mononuclear cells (PBMCs) was determined by flow cytometry and RT-PCR. Changes in Wnt/β-catenin signaling were evaluated using Western blot. Immunofluorescence staining and western blot were employed to examine NLRP3 inflammasome activation in the thyroid. YH minimized thyroid follicle injury and decreased concentrations of serum TgAb, TPOAb, TSH, T3, and T4 in EAT model. The mRNA of IL-35 was increased after YH treatment. YH also increased the percentage of Treg cells, and decreased Th17 proportion as well as Th17/Treg ratio in PBMCs. Meanwhile, the mRNA levels of Th17 related cytokines (RORγt, IL-17A, IL-21, and IL-22) were suppressed and Treg related cytokines (FoxP3, TGF-β, and IL-10) were promoted in PBMCs. Additionally, the protein expressions of Wnt-1 and β-catenin were unregulated after YH treatment. NLRP3 immunostaining signal and protein levels of IL-17, p-NF-κB, NLRP3, ASC, cleaved-Caspase-1, cleaved-IL-1β, and IL-18 were downregulated in the thyroid after YH intervention. Overall, the present study demonstrated that YH alleviated autoimmune thyroiditis in rats by improving NLRP3 inflammasome and immune dysregulation.

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Regenerative potentials of the murine thyroid in experimental autoimmune thyroiditis: role of CD24.

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