Reversal of Abnormal CD4+ T Cell Metabolism Alleviates Thyroiditis by Deactivating the mTOR/HIF1a/Glycolysis Pathway.
Reversal of Abnormal CD4+ T Cell Metabolism Alleviates Thyroiditis by Deactivating the mTOR/HIF1a/Glycolysis Pathway.
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逆转异常 CD4 T 细胞代谢，通过停用 mTOR/HIF1a/糖酵解途径缓解甲状腺炎
DOI：
10.3389/fendo.2021.659738
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发表时间：
2021
影响因子：
5.2
通讯作者：
Teng W
中科院分区：
文献类型：
--
作者：
Zhao L;Wu Q;Wang X;Wang S;Shi X;Shan Z;Teng W
桥本甲状腺炎（HT）是一种自身免疫性疾病，其特征是甲状腺抗原特异性辅助T细胞活化。HT患者Th 1和Th 17 T细胞亚群增加。糖酵解支持Th 1和Th 17 T细胞的慢性激活，但这如何有助于HT仍然未知。通过测定细胞外酸化率（ECAR）和耗氧率（OCR），对30例HT患者和30例健康对照者的CD 4 + T细胞代谢进行了评价。亚急性甲状腺炎（SAT）模型中的小鼠接受2DG、二甲双胍或联合给药。Western blot和Seahorse法检测mTOR/HIF-1α/HK 2/糖酵解的表达。采用流式细胞术和HE染色检测SAT的严重程度。HT患者的CD 4 + T细胞ECAR和OCR增强。培养的HT CD 4 + T细胞中Glut 1、HK 2、PKM 2和LDHA水平升高。与对照组相比，培养的SAT CD 4 + T细胞中HK 2和PKM 2的表达升高。mTOR和HIF-1α通路在SAT小鼠中活化显著，2DG处理组中HIF-1α表达降低。2DG和/或二甲双胍治疗显着降低了Th 17和Th 1 T细胞的比例。甲状腺炎导致CD 4 + T细胞中mTOR/HIF-1α/HK 2/糖酵解途径升高。2DG和二甲双胍治疗可降低该途径的激活，也可逆转CD 4 + T细胞分化的失衡。
Hashimoto’s thyroiditis (HT) is an autoimmune disease that features activation of thyroid antigen-specific helper T cells. HT patients have increased Th1 and Th17 T cell subsets. Glycolysis supports chronic activation of Th1 and Th17 T cells, but how this contributes to HT remains unknown. The metabolism of CD4+ T cells from 30 HT patients and 30 healthy controls was evaluated by determining the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). Mice in a subacute thyroiditis (SAT) model were treated with 2DG, metformin, or combination. Metrics of mTOR/HIF-1α/HK2/glycolysis were measured by western blot and Seahorse assay methods. The severity of SAT was measured by flow cytometry and HE staining. CD4+ T cells from HT patients had enhanced ECAR and OCR. Levels of Glut1, HK2, PKM2, and LDHA in cultured HT CD4+ T cells were elevated. The expression of HK2 and PKM2 in cultured SAT CD4+ T cells was elevated compared with the control group. Activation of the mTOR and HIF-1α pathways was significant in SAT mice, and expression of HIF-1α in the 2DG treated group was reduced. Treatment with 2DG and/or metformin significantly decreased the ratio of Th17 and Th1 T cells. Thyroiditis results in elevation of the mTOR/HIF-1α/HK2/glycolysis pathway in CD4+ T cells. The activation of this pathway is reduced by treatment with 2DG and metformin, which also reverted imbalances in CD4+ T cell differentiation.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
32.4
作者：
Weinberg, Samuel E.;Sena, Laura A.;Chandel, Navdeep S.
通讯作者：
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影响因子：
64.5
作者：
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影响因子：
6.6
作者：
Liu, Yongping;Cui, Xuejiao;Teng, Weiping
通讯作者：
Teng, Weiping
DOI：
10.1073/pnas.1420419112
发表时间：
2015-03-03
影响因子：
11.1
作者：
Liu, Guangwei;Bi, Yujing;Yang, Ruifu
通讯作者：
Yang, Ruifu