小柯机器人

美国哈佛医学院Dennis L. Kasper等研究人员合作发现，肠道共生菌群能够通过膳食氨基酸产生调节宿主免疫的脂质。相关论文于2021年11月10日在线发表在《自然》杂志上。

研究人员使用靶向脂质组分析和合成方法，对来自人类共生体脆弱拟杆菌（Bacteroides fragilis）的免疫调节性α-半乳糖基神经酰胺（BfaGCs）进行了多方面的调查。BfaGCs的特征性末端支链是脆弱拟杆菌在宿主肠道中吸收支链氨基酸的结果。一个不能代谢支链氨基酸的脆弱拟杆菌基因敲除株显示BfaGCs的支链减少，并且只定植这种突变株的小鼠的自然杀伤T（NKT）细胞调节功能受损，这意味着结构特异的免疫调节活性。BfaGCs的鞘氨醇链支链是NKT细胞激活的一个关键决定因素，它能诱导特定的免疫调节基因表达特征和效应功能。CD1d-BfaGC-NKT细胞受体复合物的共结晶结构和亲和力分析证实了BfaGCs作为CD1d限制性配体的互动。

研究人员提出了一个通过内生代谢物与饮食、微生物群和免疫系统的相互作用实现免疫调节控制的新范式。

据介绍，来自共生微生物群的小分子对肠道免疫的成熟和调节起着至关重要的作用。然而，对于在宿主-微生物群环境中控制免疫发展的分子机制知之甚少。

附：英文原文

Title: Host immunomodulatory lipids created by symbionts from dietary amino acids

Author: Oh, Sungwhan F., Praveena, T., Song, Heebum, Yoo, Ji-Sun, Jung, Da-Jung, Erturk-Hasdemir, Deniz, Hwang, Yoon Soo, Lee, ChangWon C., Le Nours, Jrme, Kim, Hyunsoo, Lee, Jesang, Blumberg, Richard S., Rossjohn, Jamie, Park, Seung Bum, Kasper, Dennis L.

Issue&Volume: 2021-11-10

Abstract: Small molecules derived from symbiotic microbiota critically contribute to intestinal immune maturation and regulation1. However, little is known about the molecular mechanisms that control immune development in the host–microbiota environment. Here, using a targeted lipidomic analysis and synthetic approach, we carried out a multifaceted investigation of immunomodulatory α-galactosylceramides from the human symbiont Bacteroides fragilis (BfaGCs). The characteristic terminal branching of BfaGCs is the result of incorporation of branched-chain amino acids taken up in the host gut by B. fragilis. A B. fragilis knockout strain that cannot metabolize branched-chain amino acids showed reduced branching in BfaGCs, and mice monocolonized with this mutant strain had impaired colonic natural killer T (NKT) cell regulation, implying structure-specific immunomodulatory activity. The sphinganine chain branching of BfaGCs is a critical determinant of NKT cell activation, which induces specific immunomodulatory gene expression signatures and effector functions. Co-crystal structure and affinity analyses of CD1d–BfaGC–NKT cell receptor complexes confirmed the interaction of BfaGCs as CD1d-restricted ligands. We present a structural and molecular-level paradigm of immunomodulatory control by interactions of endobiotic metabolites with diet, microbiota and the immune system.

DOI: 10.1038/s41586-021-04083-0

Source: https://www.nature.com/articles/s41586-021-04083-0

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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