Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes.
Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes.
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DOI：
10.1016/j.celrep.2021.109447
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发表时间：
2021-07-27
期刊：
影响因子：
8.8
通讯作者：
Cho, Young Min
中科院分区：
文献类型：
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作者：
Kong, Byung Soo;Min, Se Hee;Lee, Changhan;Cho, Young Min
线粒体是主要的代谢细胞器，越来越多地被揭示为免疫调节剂。然而，目前还不知道是否p53编码的肽调节T细胞诱导表型和功能的变化。在这里，我们发现MOTS-c通过NOD小鼠（一种1型糖尿病（T1 D）动物模型）中T细胞的表型和功能变化来防止自身免疫性β细胞破坏。MOTS-c改善高血糖症的发展并减少胰岛浸润免疫细胞。此外，从MOTS-c处理的NOD小鼠过继转移T细胞显著降低了NOD-SCID小鼠的糖尿病发病率。代谢和基因组分析显示MOTS-c通过调节TCR/mTORC 1通路调节T细胞表型和功能。我们观察到T1 D患者的血清MOTS-c水平低于健康对照组。此外，MOTS-c通过减轻T1 D患者中T细胞的糖酵解应激来减少T细胞活化，这表明了潜在的治疗意义。我们的研究结果表明，MOTS-c作为调节T细胞表型和功能的自身免疫性糖尿病。
Mitochondria are principal metabolic organelles that are increasingly unveiled as immune regulators. However, it is currently not known whether mitochondrial-encoded peptides modulate T cells to induce changes in phenotype and function. Here, we found that MOTS-c prevented autoimmune β-cell destruction via phenotypical and functional changes of T cells in NOD mice, a type 1 diabetes (T1D) animal model. MOTS-c ameliorated the development of hyperglycemia and reduced islet-infiltrating immune cells. Furthermore, adoptive transfer of T cells from MOTS-c-treated NOD mice significantly decreased the incidence of diabetes in NOD-SCID mice. Metabolic and genomic analysis revealed that MOTS-c modulated T cell phenotype and function by regulating TCR/mTORC1 pathway. We observed that T1D patients had a lower serum MOTS-c level than healthy controls. Furthermore, MOTS-c reduced T cell activation by alleviating T cells from the glycolytic stress in T1D patients suggesting a potential therapeutic implication. Our findings indicate that the MOTS-c acts as a regulator of T cell phenotype and function in autoimmune diabetes.
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影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
11.2
作者：
Bergmann, Christoph;Strauss, Laura;Whiteside, Theresa L.
通讯作者：
Whiteside, Theresa L.
影响因子：
56.9
作者：
Chong, AS;Shen, JK;Philipson, LH
通讯作者：
Philipson, LH
影响因子：
7.7
作者：
CHRISTIANSON, SW;SHULTZ, LD;LEITER, EH
通讯作者：
LEITER, EH
DOI：
10.1038/nri3198
发表时间：
2012-04-20
期刊：
Nature reviews. Immunology
影响因子：
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作者：
通讯作者：
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