The aberrant tonsillar microbiota modulates autoimmune responses in rheumatoid arthritis
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
- Yuanjie Zhou (ORCID: https://orcid.org/0000-0003-1254-1819)
- Wenjing Xiao (ORCID: https://orcid.org/0000-0001-7037-9229)
- Xuanlin Cai
- Lijun Wu (ORCID: https://orcid.org/0000-0001-5876-8379)
- Yuan An (ORCID: https://orcid.org/0000-0002-8686-2140)
- Ruochun Guo (ORCID: https://orcid.org/0000-0002-0322-3264)
- Zhanguo Li (ORCID: https://orcid.org/0000-0002-3421-6972)
- Fanlei Hu (ORCID: https://orcid.org/0000-0002-3892-3164)
- Peishi Rao
- Xiaohong Xiang (ORCID: https://orcid.org/0000-0002-9020-9187)
- Xiaolin Sun (ORCID: https://orcid.org/0000-0001-9709-1532)
- Rentao Yang
- Yuebo Jin (ORCID: https://orcid.org/0000-0003-3379-8998)
- Lulu Cao (ORCID: https://orcid.org/0009-0000-0088-5919)
- Jianping Guo (ORCID: https://orcid.org/0000-0002-5031-3510)
- Jing Li (ORCID: https://orcid.org/0000-0003-2504-1629)
- Xuan Zhang (ORCID: https://orcid.org/0000-0001-8775-1699)
- Hua Ye (ORCID: https://orcid.org/0000-0002-4947-6195)
- Shenghui Li (ORCID: https://orcid.org/0000-0003-1071-8510)
- Binbin Xia
- Jing He (ORCID: https://orcid.org/0000-0003-3904-8928)
- Yuan Jia (ORCID: https://orcid.org/0000-0002-7928-3917)
- Junjie Qin (ORCID: https://orcid.org/0000-0001-5893-2271)
- Jiayang Jin (ORCID: https://orcid.org/0000-0001-8791-3192)
- Yan Zhong
- Jun Wang (ORCID: https://orcid.org/0000-0002-6278-0677)
Institutions
- Chinese Academy of Sciences (CN)
- Peking University (CN)
- People's Hospital of Xinjiang Uygur Autonomous Region (CN)
- Peking University People's Hospital (CN)
- Institute of Microbiology (CN)
- Center for Life Sciences (CN)
- University of Chinese Academy of Sciences (CN)
- China Agricultural University (CN)
Publication Details
- Journal
- JCI Insight
- Published
- 2024-08-20
- DOI
- https://doi.org/10.1172/jci.insight.175916
- Citations
- 13
- Primary Topic
- Ginseng Biological Effects and Applications
- Type
- article
- Field-Weighted Citation Impact
- 3.04
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Peking University
- Beijing Municipal Science and Technology Commission
- Foundation for Innovative Research Groups of the National Natural Science Foundation of China
- Peking University People's Hospital
- National Key Research and Development Program of China
- Institute of Microbiology, Chinese Academy of Sciences