小柯机器人

日本理化学研究所Sidonia Fagarasan小组发现，B细胞产生的GABA激发IL-10⁺ 巨噬细胞来限制抗肿瘤免疫力。相关论文于2021年11月3日在线发表在《自然》杂志上。

研究人员发现，代谢物和神经递质GABA是由活化的B细胞和浆细胞合成和分泌的候选信号分子。结果表明，B细胞衍生的GABA促进单核细胞分化为抗炎巨噬细胞，分泌白细胞介素-10并抑制CD8⁺ T细胞杀伤功能。在小鼠中，B细胞缺乏或B细胞特异性失活的GABA生成酶GAD67会增强抗肿瘤反应。这项研究显示，除了细胞因子和膜蛋白外，来自B系细胞的小型代谢物也具有免疫调节功能，这可能是能够对免疫反应进行微调的成药靶标。

据介绍，小型的可溶性代谢物不仅是细胞内生化过程中的重要中间体，而且在释放到细胞外环境中时也能影响邻近的细胞。

附：英文原文

Title: B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity

Author: Zhang, Baihao, Vogelzang, Alexis, Miyajima, Michio, Sugiura, Yuki, Wu, Yibo, Chamoto, Kenji, Nakano, Rei, Hatae, Ryusuke, Menzies, Rosemary J., Sonomura, Kazuhiro, Hojo, Nozomi, Ogawa, Taisaku, Kobayashi, Wakana, Tsutsui, Yumi, Yamamoto, Sachiko, Maruya, Mikako, Narushima, Seiko, Suzuki, Keiichiro, Sugiya, Hiroshi, Murakami, Kosaku, Hashimoto, Motomu, Ueno, Hideki, Kobayashi, Takashi, Ito, Katsuhiro, Hirano, Tomoko, Shiroguchi, Katsuyuki, Matsuda, Fumihiko, Suematsu, Makoto, Honjo, Tasuku, Fagarasan, Sidonia

Issue&Volume: 2021-11-03

Abstract: Small, soluble metabolites not only are essential intermediates in intracellular biochemical processes, but can also influence neighbouring cells when released into the extracellular milieu1,2,3. Here we identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells. We show that B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8+ T cell killer function. In mice, B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses. Our study reveals that, in addition to cytokines and membrane proteins, small metabolites derived from B-lineage cells have immunoregulatory functions, which may be pharmaceutical targets allowing fine-tuning of immune responses.

DOI: 10.1038/s41586-021-04082-1

Source: https://www.nature.com/articles/s41586-021-04082-1

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