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

• DOI: 10.1002/advs.202202706
• Publication Date: 2022-08-29T01:45:48Z
• Authors: 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
• Keywords: rheumatoid arthritis; 0301 basic medicine; Interleukin-6; tonsillar microbiome; Science; Microbiota; Q; Palatine Tonsil; T-Lymphocytes, Helper-Inducer; Receptors, Interleukin-6; Arthritis, Rheumatoid; Mice; 03 medical and health sciences; lantibiotics; Bacteriocins; Animals; Humans; Receptors, Interleukin-21; salivaricins; IL‐6 and IL‐21 receptor; Research Articles

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