英国伦敦大学学院Claudia Mauri、Elizabeth C. Rosser等研究人员合作取得一项新进展，他们的研究表明，微生物群来源的代谢物通过介导调节性B细胞（Breg）的芳烃受体激活来抑制关节炎。该项研究成果于2020年3月26日在线发表在《细胞—代谢》杂志上。
研究人员发现，类风湿性关节炎（RA）患者和关节炎小鼠与健康对照组相比，微生物来源的短链脂肪酸（SCFA）减少，而在小鼠中，补充SCFA丁酸盐可降低关节炎的严重程度。补充丁酸酯可通过增加血清素衍生的代谢物5-羟吲哚-3-乙酸（5-HIAA）水平来抑制Breg依赖性关节炎，这一代谢物可激活调控Breg功能的转录标记物芳烃受体（AhR）。
因此，补充丁酸盐介导的AhR激活能够调控支持Breg功能的分子程序，同时抑制生发中心（GC）B细胞和成浆细胞分化。这项研究表明，补充丁酸盐可能用于缓解全身性自身免疫疾病。
据了解，在响应肠道微生物群来源信号后，产生IL-10的Breg能够分化出来，从而维持免疫耐受。但是，微生物来源的代谢产物是否可以调节Breg抑制功能仍不清楚。
附：英文原文
Title: Microbiota-Derived Metabolites Suppress Arthritis by Amplifying Aryl-Hydrocarbon Receptor Activation in Regulatory B Cells
Author: Elizabeth C. Rosser, Christopher J.M. Piper, Diana E. Matei, Paul A. Blair, André F. Rendeiro, Michael Orford, Dagmar G. Alber, Thomas Krausgruber, Diego Catalan, Nigel Klein, Jessica J. Manson, Ignat Drozdov, Christoph Bock, Lucy R. Wedderburn, Simon Eaton, Claudia Mauri
Issue&Volume: 2020-03-25
Abstract: The differentiation of IL-10-producing regulatory B cells (Bregs) in response to gut-microbiota-derived signals supports the maintenance of tolerance. However, whether microbiota-derived metabolites can modulate Breg suppressive function remains unknown. Here, we demonstrate that rheumatoid arthritis (RA) patients and arthritic mice have a reduction in microbial-derived short-chain fatty acids (SCFAs) compared to healthy controls and that in mice, supplementation with the SCFA butyrate reduces arthritis severity. Butyrate supplementation suppresses arthritis in a Breg-dependent manner by increasing the level of the serotonin-derived metabolite 5-Hydroxyindole-3-acetic acid (5-HIAA), which activates the aryl-hydrocarbon receptor (AhR), a newly discovered transcriptional marker for Breg function. Thus, butyrate supplementation via AhR activation controls a molecular program that supports Breg function while inhibiting germinal center (GC) B cell and plasmablast differentiation. Our study demonstrates that butyrate supplementation may serve as a viable therapy for the amelioration of systemic autoimmune disorders.
DOI: 10.1016/j.cmet.2020.03.003
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30118-2
Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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本期文章：《细胞—代谢》：Online/在线发表
