Reversal of Abnormal CD4+ T Cell Metabolism Alleviates Thyroiditis by Deactivating the mTOR/HIF1a/Glycolysis Pathway
| العنوان: | Reversal of Abnormal CD4+ T Cell Metabolism Alleviates Thyroiditis by Deactivating the mTOR/HIF1a/Glycolysis Pathway |
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| المؤلفون: | Shiqi Wang, Zhongyan Shan, Qiong Wu, Xiaoli Wang, Xiaoguang Shi, Lei Zhao, Weiping Teng |
| المصدر: | Frontiers in Endocrinology Frontiers in Endocrinology, Vol 12 (2021) |
| بيانات النشر: | Frontiers Media S.A., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, T cell, immunometabolism, Tregs, Hashimoto Disease, HIF1a, Deoxyglucose, Thyroiditis, Diseases of the endocrine glands. Clinical endocrinology, Autoimmune thyroiditis, 03 medical and health sciences, Mice, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Animals, Humans, Glycolysis, Thyroiditis, Subacute, PI3K/AKT/mTOR pathway, Original Research, Aged, Glucose Transporter Type 1, Chemistry, TOR Serine-Threonine Kinases, Thyroid, Hashimoto’s thyroiditis, glycolysis, Middle Aged, Th1 Cells, medicine.disease, RC648-665, Hypoxia-Inducible Factor 1, alpha Subunit, Metformin, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, T cell differentiation, Th17 Cells, Female, medicine.drug, Signal Transduction |
| الوصف: | BackgroundHashimoto’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.MethodsThe 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.ResultsCD4+ 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.ConclusionsThyroiditis 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. |
| اللغة: | English |
| تدمد: | 1664-2392 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9dd9f08d28f4f66078993065e54d45caTest http://europepmc.org/articles/PMC8211914Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9dd9f08d28f4f66078993065e54d45ca |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16642392 |
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