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A new role of diacylglycerol kinase α on the secretion of lethal exosomes bearing Fas ligand during activation-induced cell death of T lymphocytes

机译:二酰基甘油激酶α在活化诱导的T淋巴细胞死亡过程中对Fas配体致死性外泌体分泌的新作用

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摘要

Exosomes are small membrane vesicles that intracellularly accumulate into late or multivesicular endosomes (multivesicular bodies, MVB). Exosomes have a particular lipid and protein content, reflecting their origin as intraluminal vesicles of late endosomes. The stimulation of several hematopoietic cells induces the fusion of the limiting membrane of the MVB with the plasma membrane, leading to the release of exosomes towards the extracellular environment. In T lymphocytes, stimulation of the T cell receptor (TCR) induces the fusion of the MVBs with the plasma membrane and exosomes carrying several bio-active proteins are secreted. Among these proteins, the pro-apoptotic protein Fas ligand (FasL) is released as a non-proteolysed form (mFasL), associated to the exosomes. These mFasL-bearing exosomes may trigger the apoptosis of T lymphocytes. Here, we present evidences supporting a role of diacylglycerol kinase α (DGKα), a diacylglycerol (DAG)-consuming enzyme, on the secretion of exosomes carrying mFasL, and the subsequent activation-induced cell death (AICD) on a T cell line and primary T lymphoblasts.
机译:外泌体是细胞内积累到晚期或多囊泡内体(多囊泡体,MVB)中的小膜囊泡。外泌体具有特定的脂质和蛋白质含量,反映出它们起源于晚期内体的腔内囊泡。几个造血细胞的刺激诱导MVB的限制膜与质膜的融合,导致外来体向细胞外环境的释放。在T淋巴细胞中,对T细胞受体(TCR)的刺激会诱导MVB与质膜融合,并且会分泌带有几种生物活性蛋白的外泌体。在这些蛋白质中,促凋亡蛋白Fas配体(FasL)以非蛋白水解形式(mFasL)释放,与外泌体相关。这些带有mFasL的外泌体可能触发T淋巴细胞的凋亡。在这里,我们提供证据支持消耗二酰基甘油(DAG)的双酰基甘油激酶α(DGKα)在携带mFasL的外泌体分泌以及随后在T细胞系和细胞上的激活诱导的细胞死亡(AICD)的作用。原发性T淋巴母细胞。

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