Circulation：免疫蛋白酶体抑制剂可减轻自体免疫相关性心肌炎的心脏特异性免疫反应

2020-06-13 MedSci原创 MedSci原创

免疫检查点抑制剂(ICI)治疗常伴有免疫相关病理，高危型ICI相关性心肌炎的发生率增高。解析这种副作用所涉及的机制可以使管理策略的发展成为可能。

免疫检查点抑制剂(ICI)治疗常伴有免疫相关病理，高危型ICI相关性心肌炎的发生率增高。解析这种副作用所涉及的机制可以使管理策略的发展成为可能。在小鼠模型中，免疫检查点(如PD-1)可调节靶向心脏TnI(肌钙蛋白I)的自我抗原反应的阈值。本研究目的是研究免疫蛋白酶体（免疫细胞的主要蛋白水解机制，在LMP2中有3种不同的蛋白酶活性）和MECL1亚基（多细胞催化内肽酶复合物亚基1）是如何影响TnI介导的心脏自身免疫病理。 TnI介导的自身免疫性心肌炎（TnI-AM），一种CD4+T细胞介导的疾病，小鼠缺乏3种免疫蛋白酶体亚基或缺失编码LMP2或LMP7的基因时，会诱导出该疾病。在诱导TnI-AM前，或建立了自身免疫性心肌炎后，用免疫蛋白酶体抑制剂ONX0914处理小鼠。所有免疫蛋白酶体缺陷品系的小鼠都表现出减轻的自身免疫相关性心脏病理，如炎症较轻、促炎因子和细胞因子水平较低、IL-17的合成较少以及心肌纤维化减轻。LMP7-/-小鼠的TnI-介导的自身免疫性心脏病理的保护作用与脾脏中调节CD4+T细胞和效应体之间的平衡变化相关；LMP7-/-小鼠来源的调节CD4+T细胞的抑制PD-1分子

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2021-05-26 jklm09

#抑制剂#

26 0
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2020-07-18 canlab

#蛋白酶#

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2020-09-13 shenxlcyp

#相关性#

29 0
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2020-09-20 changjitao2017

#蛋白酶体抑制剂#

40 0
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2020-09-23 jinweidong

#特异性#

18 0
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2020-12-27 gds2009

#蛋白酶体#

21 0
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2020-06-29 122e052cm96暂无昵称

好

72 0
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2020-06-15 cnxcy

#免疫反应#

23 0

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