Dietary protein modulates intestinal dendritic cells to establish mucosal homeostasis

IF 7.9 2区 医学 Q1 IMMUNOLOGY
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引用次数: 0

Abstract

Dietary proteins are taken up by intestinal dendritic cells (DCs), cleaved into peptides, loaded to major histocompatibility complexes, and presented to T cells to generate an immune response. Amino acid (AA)-diets do not have the same effects because AAs cannot bind to major histocompatibility complex to activate T cells. Here, we show that impairment in regulatory T cell generation and loss of tolerance in mice fed a diet lacking whole protein is associated with major transcriptional changes in intestinal DCs including downregulation of genes related to DC maturation, activation and decreased gene expression of immune checkpoint molecules. Moreover, the AA-diet had a profound effect on microbiome composition, including an increase in Akkermansia muciniphilia and Oscillibacter and a decrease in Lactococcus lactis and Bifidobacterium. Although microbiome transfer experiments showed that AA-driven microbiome modulates intestinal DC gene expression, most of the unique transcriptional change in DC was linked to the absence of whole protein in the diet. Our findings highlight the importance of dietary proteins for intestinal DC function and mucosal tolerance.
膳食蛋白质调节肠道树突状细胞,建立粘膜稳态。
膳食蛋白质会被肠道树突状细胞(DC)吸收,裂解成肽,装载到主要组织相容性配体(MHC)上,并呈现给 T 细胞以产生免疫反应。氨基酸(AA)饮食没有同样的效果,因为AA不能与MHC结合以激活T细胞。在这里,我们发现,以缺乏全蛋白的饮食喂养的小鼠的 Treg 细胞生成障碍和耐受性丧失与肠道 DC 的主要转录变化有关,包括 DC 成熟、活化和迁移相关基因的下调以及免疫检查点分子基因表达的减少。此外,AA饮食对微生物组的组成也有深远影响,包括Akkermansia muciniphilia和Oscillibacter的增加以及乳酸乳球菌和双歧杆菌的减少。虽然微生物组转移实验表明 AA 驱动的微生物组会调节肠道直肠基因表达,但直肠中大多数独特的转录变化都与膳食中缺乏全蛋白质有关。我们的研究结果凸显了膳食蛋白质对肠道直流电功能和粘膜耐受性的重要性。
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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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