Bcl-3 regulates the function of Th17 cells through raptor mediated glycolysis metabolism.
Bcl-3 regulates the function of Th17 cells through raptor mediated glycolysis metabolism.
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Bcl-3通过raptor介导的糖酵解代谢调节Th17细胞的功能
DOI：
10.3389/fimmu.2022.929785
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
Bcl - 3是一种非典型的IκB家族成员，它通过与p50 / p52同源二聚体亚基结合来调节细胞核中的转录。尽管各种研究阐明了Bcl - 3在生理功能中的重要作用，但其在代谢中的作用仍不清楚。我们发现Bcl - 3对自身免疫具有代谢调节作用。Bcl - 3缺失的小鼠无法发生实验性自身免疫性脑脊髓炎。这种抗病性与Th17细胞中乳酸水平的升高有关，并且乳酸能够缓解野生型小鼠实验性自身免疫性脑脊髓炎的发展。Bcl - 3缺陷小鼠具有更多分化的Th17细胞，并且这些细胞的细胞外酸化率增加。同时，它们的最终呼吸速率和呼吸储备能力明显低于野生型小鼠。然而，向Bcl - 3缺陷的Th17细胞中添加GNE - 140（乳酸脱氢酶抑制剂）可以逆转这种现象，并且补充乳酸可以增加野生型小鼠Th17细胞的糖酵解代谢。从机制上讲，Bcl - 3可以通过ANK和RNC结构域与Raptor相互作用。因此，Bcl - 3通过促进Raptor介导的能量代谢来调节Th17的致病性，揭示了一种对适应性免疫的新型调节机制。
Bcl-3 is an atypical IκB family member that regulates transcription in the nucleus by binding to the p50/p52 homologous dimer subunit. Although various studies illustrate the important role of Bcl-3 in physiological function, its role in metabolism is still unclear. We found that Bcl-3 has a metabolic regulatory effect on autoimmunity. Bcl-3-depleted mice are unable to develop experimental autoimmune encephalomyelitis. The disease resistance was linked to an increase in lactate levels in Th17 cells, and lactate could alleviate EAE development in WT mice. Bcl-3 deficient mice had more differentiated Th17 cells and an increased extracellular acidification rate in these cells. Concurrently, their ultimate respiration rate and respiratory reserve capacity were significantly lower than wild-type mice. However, adding GNE-140 (LADH inhibitor) to Bcl-3-deficient Th17 cells could reverse the phenomenon, and lactate supplementation could increase the glycolysis metabolism of Th17 cells in WT mice. Mechanically, Bcl-3 could interact with Raptor through ANK and RNC domains. Therefore, Bcl-3 regulates Th17 pathogenicity by promoting Raptor mediated energy metabolism, revealing a novel regulation of adaptive immunity.
影响因子：
7.7
作者：
Ruan Q;Zheng SJ;Palmer S;Carmody RJ;Chen YH
通讯作者：
Chen YH