The aberrant tonsillar microbiota modulates autoimmune responses in rheumatoid arthritis

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Abstract

Palatine tonsils are the only air-contacted lymphoid organs that constantly engage in crosstalk with commensal microorganisms and serve as the first handling sites against microbial antigens. While tonsil inflammations have been implicated in various autoimmune diseases, including rheumatoid arthritis (RA), the precise role of tonsillar microbiota in autoimmune pathogenesis remains inadequately characterized. In this study, we profiled the tonsillar microbiota and identified a notable dysbiosis in patients with RA, particularly within the Streptococcus genus. Specifically, patients with RA exhibited an enrichment of pathogenic Streptococcus species, including S. pyogenes, S. dysgalactiae, and S. agalactiae. Colonization with these bacteria significantly exacerbated arthritis severity and increased autoimmune responses in collagen-induced arthritis (CIA). Furthermore, immunization with peptides derived from these pathogenic Streptococcus species directly induced experimental arthritis. Conversely, patients with RA demonstrated a marked deficiency in commensal Streptococcus members, notably S. salivarius. Treatment of CIA mice with S. salivarius attenuated the progression of arthritis and downregulated autoimmune responses. These findings highlight a pathogenic link of tonsillar microbiota with RA, shedding light on their contribution to autoimmunity.

Authors

Jing Li, Shenghui Li, Jiayang Jin, Ruochun Guo, Yuebo Jin, Lulu Cao, Xuanlin Cai, Peishi Rao, Yan Zhong, Xiaohong Xiang, Xiaolin Sun, Jianping Guo, Fanlei Hu, Hua Ye, Yuan Jia, Wenjing Xiao, Yuan An, Xuan Zhang, BinBin Xia, Rentao Yang, Yuanjie Zhou, Lijun Wu, Junjie Qin, Jing He, Jun Wang, Zhanguo Li