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B细胞衍生GABA诱导IL-10+巨细胞限制抗瘤免疫力

Baihao Zhang¹, Alexis Vogelzang¹, Michio Miyajima¹

¹Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute, Yokohama, Japan.

|November 4, 2021

概括

通过促进抗炎性巨细胞,抑制抗瘤免疫力. 抑制B细胞中的GABA产生增强了抗瘤反应.

科学领域:

免疫学
神经科学
代谢学

背景情况:

包括代谢物和神经递质在内的小分子在细胞通信中起着至关重要的作用.
细胞外代谢物可以影响细胞内生化过程之外的细胞功能.
B细胞和血细胞是适应性免疫的关键参与者,传统上以产生抗体而闻名.

研究的目的:

通过激活的B细胞分泌的新信号分子.
研究由B细胞产生的代谢物氨酸 (GABA) 的免疫调节作用.
探索针对B细胞衍生GABA在免疫调节和抗瘤反应中的治疗潜力.

主要方法:

鉴定GABA作为活性B细胞和血细胞分泌的代谢物.
测试以确定B细胞衍生GABA对单细胞分化成巨细胞的影响.
评估巨细胞因子 (例如,互白素-10).
评估GABA对CD8+T细胞细胞毒性功能的影响.
使用缺乏B细胞的小鼠和针对GABA合成酶GAD67的小鼠进行体内研究以评估抗瘤免疫力.

主要成果:

激活的B细胞和血细胞合成和分泌神经递质氨酸 (GABA).
B细胞衍生GABA促进单细胞分化为抗炎巨细胞.
这些巨细胞分泌interleukin-10并抑制CD8+T细胞杀伤活性.
在小鼠模型中,B细胞缺乏或GABA合成受损导致抗瘤免疫反应增强.

结论:

乙系细胞分泌代谢物GABA,该代谢物充当免疫调节分子.
B细胞衍生GABA有助于免疫抑制,特别是在抗瘤免疫的背景下.
针对B细胞的GABA产生或信号传递是调节免疫反应和增强抗癌治疗的潜在治疗策略.

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