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低剂量白介素 2 可塑造出具有免疫耐受性的肠道微生物群，从而改善自身免疫和肠道炎症。

Low-dose IL-2 shapes a tolerogenic gut microbiota that improves autoimmunity and gut inflammation.

机构信息

Sorbonne Université, INSERM, Immunology-Immunopathology-Immunotherapy (i3), Paris, France.

AP-HP, Hôpital Pitié-Salpêtrière, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (i2B), Paris, France.

出版信息

JCI Insight. 2022 Sep 8;7(17):e159406. doi: 10.1172/jci.insight.159406.

DOI:10.1172/jci.insight.159406
PMID:35917175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9536277/
Abstract

Gut microbiota dysbiosis is associated with inflammatory bowel diseases and with cardiometabolic, neurological, and autoimmune diseases. Gut microbiota composition has a direct effect on the immune system, and vice versa, and it has a particular effect on Treg homeostasis. Low-dose IL-2 (IL-2LD) stimulates Tregs and is a promising treatment for autoimmune and inflammatory diseases. We aimed to evaluate the impact of IL-2LD on gut microbiota and correlatively on the immune system. We used 16S ribosomal RNA profiling and metagenomics to characterize gut microbiota of mice and humans treated or not with IL-2LD. We performed fecal microbiota transplantation (FMT) from IL-2LD-treated to naive recipient mice and evaluated its effects in models of gut inflammation and diabetes. IL-2LD markedly affected gut microbiota composition in mice and humans. Transfer of an IL-2-tuned microbiota by FMT protected C57BL/6J mice from dextran sulfate sodium-induced colitis and prevented diabetes in NOD mice. Metagenomic analyses highlighted a role for several species affected by IL-2LD and for microbial pathways involved in the biosynthesis of amino acids, short-chain fatty acids, and L-arginine. Our results demonstrate that IL-2LD induced changes in gut microbiota that are involved in the immunoregulatory effects of IL-2LD and suggest a crosstalk between Tregs and gut microbiota. These results provide potentially novel insight for understanding the mode of action of Treg-directed therapies.

摘要

肠道微生物失调与炎症性肠病以及代谢性、神经和自身免疫性疾病有关。肠道微生物组成对免疫系统有直接影响，反之亦然，它对 Treg 稳态有特殊影响。低剂量白细胞介素 2（IL-2LD）可刺激 Treg，是治疗自身免疫和炎症性疾病的有前途的方法。我们旨在评估 IL-2LD 对肠道微生物群的影响，以及与免疫系统的相关性。我们使用 16S 核糖体 RNA 分析和宏基因组学来描述接受或不接受 IL-2LD 治疗的小鼠和人类的肠道微生物群。我们从接受 IL-2LD 治疗的小鼠中进行粪便微生物群移植（FMT），并将其用于评估其在肠道炎症和糖尿病模型中的作用。IL-2LD 显著影响了小鼠和人类的肠道微生物群组成。通过 FMT 转移经过 IL-2 调节的微生物群可保护 C57BL/6J 小鼠免受葡聚糖硫酸钠诱导的结肠炎，并预防 NOD 小鼠的糖尿病。宏基因组分析强调了几种受 IL-2LD 影响的物种以及涉及氨基酸、短链脂肪酸和 L-精氨酸生物合成的微生物途径的作用。我们的研究结果表明，IL-2LD 诱导的肠道微生物群变化与 IL-2LD 的免疫调节作用有关，并提示 Treg 和肠道微生物群之间存在串扰。这些结果为理解 Treg 定向治疗的作用机制提供了潜在的新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0df/9536277/02998335615f/jciinsight-7-159406-g196.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0df/9536277/88b3638286cb/jciinsight-7-159406-g191.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0df/9536277/c16bc284aac0/jciinsight-7-159406-g192.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0df/9536277/4bc2c948c39c/jciinsight-7-159406-g193.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0df/9536277/cb2661bc6871/jciinsight-7-159406-g194.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0df/9536277/7ad843ed6af8/jciinsight-7-159406-g195.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0df/9536277/02998335615f/jciinsight-7-159406-g196.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0df/9536277/88b3638286cb/jciinsight-7-159406-g191.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0df/9536277/c16bc284aac0/jciinsight-7-159406-g192.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0df/9536277/4bc2c948c39c/jciinsight-7-159406-g193.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0df/9536277/cb2661bc6871/jciinsight-7-159406-g194.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0df/9536277/7ad843ed6af8/jciinsight-7-159406-g195.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0df/9536277/02998335615f/jciinsight-7-159406-g196.jpg

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