γ-Secretase inhibitor ameliorates thyroid autoimmune damage via blocking Notch1 signaling and reducing γδT17 cells in EAT mice
Abstract
In order to explore if γ-secretase inhibitor can regulate γδT17 cells by blockading Notch1 signaling pathway and then affect thyroid autoimmune damage in experimental autoimmune thyroiditis (EAT) mice. Twenty-four female C57BL/6 mice, 6 to 8-week-old, were randomly divided into NC and EAT groups, and EAT group included EAT-A (pTg treated) and EAT-B (treated with DAPT before pTg) subgroups. HE staining was conducted to observe the pathological changes of thyroid tissue. ELISA was adopted to measure the concentrations of thyroglobulin antibody (TgAb) and interleukin 17A (IL-17A) in serum. The proportions of γδT17 cells were analysed by flow cytometry. The mRNA expressions of Notch1, hairy and split 1 (Hes1) and IL-17A were measured by RT-qPCR and the protein levels of Notch intracellular domain (NICD), Hes1 and IL-17A were examined by Western Blot. The titers of TgAb and IL-17A in serum, the proportions of γδT17 cells in spleen mononuclear cells (SMCs) and thyroid mononuclear cells (TMCs), the Notch1, Hes1, IL-17A mRNA and protein expressions in EAT-A mice were all increased significantly compared with NC group (all p < 0.001). However, in EAT-B group, the above indexes were all reduced significantly than those in EAT-A group (all p < 0.05), as well as the degrees of lymphocyte infiltration in thyroid were alleviated remarkably compared with EAT-A group. Additionally, γδT17 cells percentages of EAT mice were positively correlated with TgAb titers, IL-17A concentrations and Notch1 mRNA expressions. γ-secretase inhibitor is speculated to alleviate thyroid autoimmune injury in EAT by downregulating γδT17 cells via inhibition of the Notch1/Hes1 signaling pathway.
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BibTeX
@article{wang2026γsecretase,
title = {{γ-Secretase inhibitor ameliorates thyroid autoimmune damage via blocking Notch1 signaling and reducing γδT17 cells in EAT mice}},
author = {Jue Wang and Longfei Ding and Chengyan He and Hao Liu and Yiwen Li and Yujiao Zhu and Yue Li and Haibo Xue},
journal = {Endocrine Journal},
year = {2026},
month = aug,
doi = {10.1507/endocrj.ej25-0663},
url = {https://www.jstage.jst.go.jp/article/endocrj/73/8/73_EJ25-0663/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - γ-Secretase inhibitor ameliorates thyroid autoimmune damage via blocking Notch1 signaling and reducing γδT17 cells in EAT mice
AU - Jue Wang
AU - Longfei Ding
AU - Chengyan He
AU - Hao Liu
AU - Yiwen Li
AU - Yujiao Zhu
AU - Yue Li
AU - Haibo Xue
PY - 2026
DA - 2026/08/03
JO - Endocrine Journal
DO - 10.1507/endocrj.ej25-0663
UR - https://www.jstage.jst.go.jp/article/endocrj/73/8/73_EJ25-0663/_article
AB - In order to explore if γ-secretase inhibitor can regulate γδT17 cells by blockading Notch1 signaling pathway and then affect thyroid autoimmune damage in experimental autoimmune thyroiditis (EAT) mice. Twenty-four female C57BL/6 mice, 6 to 8-week-old, were randomly divided into NC and EAT groups, and EAT group included EAT-A (pTg treated) and EAT-B (treated with DAPT before pTg) subgroups. HE staining was conducted to observe the pathological changes of thyroid tissue. ELISA was adopted to measure the concentrations of thyroglobulin antibody (TgAb) and interleukin 17A (IL-17A) in serum. The proportions of γδT17 cells were analysed by flow cytometry. The mRNA expressions of Notch1, hairy and split 1 (Hes1) and IL-17A were measured by RT-qPCR and the protein levels of Notch intracellular domain (NICD), Hes1 and IL-17A were examined by Western Blot. The titers of TgAb and IL-17A in serum, the proportions of γδT17 cells in spleen mononuclear cells (SMCs) and thyroid mononuclear cells (TMCs), the Notch1, Hes1, IL-17A mRNA and protein expressions in EAT-A mice were all increased significantly compared with NC group (all p < 0.001). However, in EAT-B group, the above indexes were all reduced significantly than those in EAT-A group (all p < 0.05), as well as the degrees of lymphocyte infiltration in thyroid were alleviated remarkably compared with EAT-A group. Additionally, γδT17 cells percentages of EAT mice were positively correlated with TgAb titers, IL-17A concentrations and Notch1 mRNA expressions. γ-secretase inhibitor is speculated to alleviate thyroid autoimmune injury in EAT by downregulating γδT17 cells via inhibition of the Notch1/Hes1 signaling pathway.
SN - 1348-4540
SN - 0918-8959
ER -