Human microbiome-derived peptide affects the development of experimental autoimmune encephalomyelitis via molecular mimicry

Author:

Ma Xin,Zhang Jian,Jiang Qianling,Li Yong-Xin,Yang Guan

Abstract

AbstractBackgroundGut commensal microbiota has been identified as a potential environmental risk factor for multiple sclerosis (MS), and numerous studies have linked the commensal microorganism with the onset of MS. However, little is known about the mechanisms underlying the gut microbiome and host-immune system interaction.ResultsHere, we introduce the concept of molecular mimicry to address this issue by mining human microbial-derived peptides based on their similarity to the MHC II-TCR binding pattern of self-antigens. We analyzed 304,246 human microbiome genomes and 103 metagenomes collected from the MS cohort and identified 731 nonredundant analogs of myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). Of note, half of these analogs could bind to MHC II and interact with TCR through structural modeling of the interaction using fine-tuned AlphaFold. Among the 8 selected peptides, the peptide (P3) derived from human gut commensalAkkermansia muciniphilashows the ability to activate MOG35-55-specific CD4+T cellsin vitroand exacerbate the development of experimental autoimmune encephalomyelitis (EAE) in mice. Furthermore, dendritic cells could process and present P3 to MOG-specific CD4+T cells and activate these cells. Collectively, our data suggests the potential involvement of a MOG35-55-mimic peptide derived from the gut microbiota as a molecular trigger of EAE pathogenesis.ConclusionsOur findings offer direct evidence of how microbes can initiate the development of EAE, suggesting a potential microbiome-based therapeutic target for inhibiting the progression of MS.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3