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在由急性Alpha7尼古丁受体激活诱导的小鼠巨细胞中,TFEB介导的前炎性反应

Havisha H Honwad^1,2, Mehran Najibi¹, Jiali Shen¹

¹Department of Microbiology, University of Massachusetts Chan Medical School, 368 Plantation St., Worcester, MA 01605, United States.

Journal of leukocyte biology

|May 28, 2025

概括

巨细胞中α7尼古丁性乙胆受体 (α7nAChR) 的激活会触发转录因子TFEB,从而导致无需释放细胞因子的炎症性基因表达. 这种新的信号通路提供了对免疫调节和潜在治疗点的见解.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
神经科学是一个神经科学.

背景情况:

转录因子TFEB和TFE3调节关键的细胞过程,包括自和溶酶体生物发生.
阿尔法7尼古丁性乙胆受体 (α7nAChR) 调节巨细胞功能和免疫反应.
以前的研究表明,α7nAChR激活影响非巨细胞中的TFEB,但其在巨细胞中的作用尚不清楚.

研究的目的:

研究α7nAChR激活在小鼠巨细胞中对TFEB和TFE3的影响.
阐明了α7nAChR介导的TFEB激活背后的信号机制.
探索对炎症调节的影响.

主要方法:

用α7nAChR激动剂PNU-282987.7治疗小鼠巨细胞.
分析包括TFEB核转位,溶酶体扩张,基因表达概况和反应性氧物种 (ROS) 测量.
实验涉及α7nAChR删除和关键信号分子的药理抑制.

主要成果:

由PNU-282987诱导的α7nAChR刺激诱导了TFEB核转位和 lysosomal扩张.
观察到一种促炎性基因特征,与细胞因子分泌不结合.
TFEB的激活依赖于MCOLN1,氨酸和ROS;即使没有α7nAChR,ROS介导的TFEB激活也持续存在.
PNU-282987增加了ROS水平,有助于TFEB激活.

结论:

在巨细胞中发现了一种新的α7nAChR-TFEB信号轴.
胆固醇受体激活通过TFEB影响巨细胞炎症基因表达.
研究结果提供了对免疫调节和潜在的炎症状况治疗策略的见解.

关键词:

美国联邦税务法 (TFEB)炎症和免疫调节的作用.lysosomes 溶解体溶解体是一个细胞.巨细胞是什么?巨细胞是什么?α7 尼古丁性乙胆受体 (α7nAChR) 的使用

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