DataVXAdvanced SciencePaper
journal article·2022-10Open access

Tonsillar Microbiome‐Derived Lantibiotics Induce Structural Changes of IL‐6 and IL‐21 Receptors and Modulate Host Immunity

Jing Li, Jiayang Jin, Shenghui Li, Yan Zhong, Yuebo Jin, Xuan Zhang, Binbin Xia, Yinhua Zhu, Ruochun Guo, Xiaolin Sun, Jianping Guo, Fanlei Hu, Wenjing Xiao, Fei Huang, Hua Ye, Ru Li, Yunshan Zhou, Xiaohong Xiang, Haihong Yao, Qiulong Yan, Li Su, Lijun Wu, Tuoping Luo, Yudong Liu, Xiaohuan Guo, Junjie Qin, Hai Qi, Jing He, Jun Wang, Zhanguo Li

Advanced Science· Volume 9· Issue 30
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Abstract

Abstract Emerging evidence emphasizes the functional impacts of host microbiome on the etiopathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). However, there are limited mechanistic insights into the contribution of microbial biomolecules especially microbial peptides toward modulating immune homeostasis. Here, by mining the metagenomics data of tonsillar microbiome, a deficiency of the encoding genes of lantibiotic peptides salivaricins in RA patients is identified, which shows strong correlation with circulating immune cells. Evidence is provided that the salivaricins exert immunomodulatory effects in inhibiting T follicular helper (Tfh) cell differentiation and interleukin‐21 (IL‐21) production. Mechanically, salivaricins directly bind to and induce conformational changes of IL‐6 and IL‐21 receptors, thereby inhibiting the bindings of IL‐6 and IL‐21 to their receptors and suppressing the downstream signaling pathway. Finally, salivaricin administration exerts both prophylactic and therapeutic effects against experimental arthritis in a murine model of RA. Together, these results provide a mechanism link of microbial peptides‐mediated immunomodulation.
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Research context

OpenAlex topics: Dermatology and Skin Diseases · Salivary Gland Disorders and Functions · Asthma and respiratory diseases

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China

Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing 100044 China

Key Laboratory of Precision Nutrition and Food Quality Department of Nutrition and Health China Agricultural University Beijing 100083 China

Promegene Translational Research Institute Shenzhen 518110 China

Department of Rheumatology and Immunology People's Hospital of Xin Jiang Uygur Autonomous Region Urumqi 830001 China

CAS Key Laboratory for Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China

University of Chinese Academy of Sciences Beijing 100049 China

Peking‐Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Beijing 100871 China

Key Laboratory of Bioorganic Chemistry and Molecular Engineering Ministry of Education and Beijing National Laboratory for Molecular Science College of Chemistry and Molecular Engineering Peking University Beijing 100871 China

Emergency Department Peking University People's Hospital Beijing 100044 China

Department of Microbiology College of Basic Medical Sciences Dalian Medical University Dalian 116044 China

Center of Medical and Health Analysis Peking University Beijing 100191 China

Department of Clinical Laboratory Peking University People's Hospital Beijing 100044 China

Institute for Immunology, School of Medicine Tsinghua University Beijing 100084 China

Department of Basic Biomedical Sciences, School of Medicine, Laboratory of Dynamic Immunobiology, Tsinghua‐Peking Center for Life Sciences Tsinghua University Beijing 10084 China

State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University Beijing 100191 China

Funding

National Natural Science Foundation of China

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