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.

中文翻译：

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微生物群衍生代谢物通过放大调节性 B 细胞中的芳基烃受体激活来抑制关节炎。

产生 IL-10 的调节性 B 细胞 (Bregs) 响应肠道微生物群衍生信号的分化支持维持耐受性。然而，微生物群衍生的代谢物是否可以调节 Breg 抑制功能仍然未知。在这里，我们证明类风湿性关节炎 (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。丁酸盐补充剂通过增加血清素衍生代谢物 5-羟基吲哚-3-乙酸 (5-HIAA) 的水平以 Breg 依赖性方式抑制关节炎，该代谢物可激活芳基烃受体 (AhR)，这是一种新发现的转录标记物为 Breg 函数。因此，通过 AhR 激活补充丁酸盐可控制支持 Breg 功能的分子程序，同时抑制生发中心 (GC) B 细胞和浆母细胞分化。我们的研究表明，丁酸盐补充剂可作为改善全身性自身免疫性疾病的可行疗法。