Advanced Science (Oct 2022)
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
Affiliations
- Jing Li
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Jiayang Jin
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Shenghui Li
- Key Laboratory of Precision Nutrition and Food Quality Department of Nutrition and Health China Agricultural University Beijing 100083 China
- Yan Zhong
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Yuebo Jin
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Xuan Zhang
- CAS Key Laboratory for Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China
- Binbin Xia
- CAS Key Laboratory for Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China
- Yinhua Zhu
- Peking‐Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Beijing 100871 China
- Ruochun Guo
- Promegene Translational Research Institute Shenzhen 518110 China
- Xiaolin Sun
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Jianping Guo
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Fanlei Hu
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Wenjing Xiao
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Fei Huang
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Hua Ye
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Ru Li
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Yunshan Zhou
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Xiaohong Xiang
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Haihong Yao
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Qiulong Yan
- Department of Microbiology College of Basic Medical Sciences Dalian Medical University Dalian 116044 China
- Li Su
- Center of Medical and Health Analysis Peking University Beijing 100191 China
- Lijun Wu
- Department of Rheumatology and Immunology People's Hospital of Xin Jiang Uygur Autonomous Region Urumqi 830001 China
- Tuoping Luo
- Peking‐Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Peking University Beijing 100871 China
- Yudong Liu
- Department of Clinical Laboratory Peking University People's Hospital Beijing 100044 China
- Xiaohuan Guo
- Institute for Immunology, School of Medicine Tsinghua University Beijing 100084 China
- Junjie Qin
- Promegene Translational Research Institute Shenzhen 518110 China
- Hai Qi
- Department of Basic Biomedical Sciences, School of Medicine, Laboratory of Dynamic Immunobiology, Tsinghua‐Peking Center for Life Sciences Tsinghua University Beijing 10084 China
- Jing He
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- Jun Wang
- CAS Key Laboratory for Pathogenic Microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China
- Zhanguo Li
- Department of Rheumatology and Immunology Peking University People's Hospital Beijing 100044 China
- DOI
- https://doi.org/10.1002/advs.202202706
- Journal volume & issue
-
Vol. 9,
no. 30
pp. n/a – n/a
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.
Keywords
