Open AccessTonsillar Microbiome‐Derived Lantibiotics Induce Structural Changes of IL‐6 and IL‐21 Receptors and Modulate Host Immunity
Author(s) -
Li Jing,
Jin Jiayang,
Li Shenghui,
Zhong Yan,
Jin Yuebo,
Zhang Xuan,
Xia Binbin,
Zhu Yinhua,
Guo Ruochun,
Sun Xiaolin,
Guo Jianping,
Hu Fanlei,
Xiao Wenjing,
Huang Fei,
Ye Hua,
Li Ru,
Zhou Yunshan,
Xiang Xiaohong,
Yao Haihong,
Yan Qiulong,
Su Li,
Wu Lijun,
Luo Tuoping,
Liu Yudong,
Guo Xiaohuan,
Qin Junjie,
Qi Hai,
He Jing,
Wang Jun,
Li Zhanguo
Publication year - 2022
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202202706
Subject(s) - microbiome , immune system , receptor , biology , immunity , immunology , microbiology and biotechnology , bioinformatics , biochemistry
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 oftonsillar 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.