B cell-derived GABA elicits IL-10⁺ macrophages tolimit anti-tumour immunity
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- 章, 白浩
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute
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- フォーゲルザンク, アレクシス
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute
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- 宮島, 倫生
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute
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- 杉浦, 悠毅
- Department of Biochemistry and Integrative Biology, Keio University
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- ウー, イボ
- YCI Laboratory for Next-Generation Proteomics, Center for Integrative Medical Sciences, RIKEN Yokohama Institute
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- 茶本, 健司
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto University
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- 中野, 令
- Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, Nihon University College of Bioresource Sciences
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- 波多江, 龍亮
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto University
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- メンジーズ, ローズマリー
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto University
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- 園村, 和弘
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto University
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- 北條, 望
- Laboratory for Prediction of Cell Systems Dynamics, RIKEN Center for Biosystems Dynamics Research (BDR)
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- 小川, 泰策
- Laboratory for Prediction of Cell Systems Dynamics, RIKEN Center for Biosystems Dynamics Research (BDR)
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- 小林, 若菜
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute
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- 筒井, 裕美
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute
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- 山本, 幸子
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute
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- 丸谷, 美香子
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute
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- 成島, 聖子
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute
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- 鈴木, 敬一朗
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute
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- 杉谷, 博士
- Laboratory of Veterinary Biochemistry, Department of Veterinary Medicine, Nihon University College of Bioresource Sciences
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- 村上, 孝作
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto University
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- 橋本, 求
- Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto University
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- 上野, 英樹
- Department of Immunology, Kyoto University Graduate School of Medicine, Kyoto University
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- 小林, 恭
- Department of Urology, Kyoto University Graduate School of Medicine, Kyoto University
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- 伊藤, 克弘
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto University; Department of Urology, Kyoto University Graduate School of Medicine, Kyoto University
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- 平野, 智子
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto University
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- 城口, 克之
- Laboratory for Prediction of Cell Systems Dynamics, RIKEN Center for Biosystems Dynamics Research (BDR)
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- 松田, 文彦
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto University
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- 末松, 誠
- Department of Biochemistry and Integrative Biology, Keio University
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- 本庶, 佑
- Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto University
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- ファガラサン, シドニア
- Laboratory for Mucosal Immunity, Center for Integrative Medical Sciences, RIKEN Yokohama Institute; Division of Integrated High-Order Regulatory Systems, Center for Cancer Immunotherapy and Immunobiology, Kyoto University Graduate School of Medicine, Kyoto University
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説明
Small, soluble metabolites not only are essential intermediates in intracellular biochemical processes, but can also influence neighbouring cells when released into the extracellular milieu1-3. 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.
収録刊行物
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- Nature
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Nature 599 (7885), 471-476, 2021-11-18
Springer Nature
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詳細情報 詳細情報について
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- CRID
- 1050008688816775040
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- NII論文ID
- 120007169951
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- ISSN
- 14764687
- 00280836
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- HANDLE
- 2433/266090
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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