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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\ntonsillar 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\u201021 (IL\u201021) production. Mechanically, salivaricins directly bind to and induce conformational changes of IL\u20106 and IL\u201021 receptors, thereby inhibiting the bindings of IL\u20106 and IL\u201021 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\u2010mediated immunomodulation.<\/jats:p>","DOI":"10.1002\/advs.202202706","type":"journal-article","created":{"date-parts":[[2022,8,28]],"date-time":"2022-08-28T21:45:48Z","timestamp":1661723148000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Tonsillar Microbiome\u2010Derived Lantibiotics Induce Structural Changes of IL\u20106 and IL\u201021 Receptors and Modulate Host Immunity"],"prefix":"10.1002","volume":"9","author":[{"given":"Jing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology Peking University People's Hospital  Beijing 100044 China"},{"name":"Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135)  Beijing 100044 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