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The aberrant tonsillar microbiota modulates autoimmune responses in rheumatoid arthritis
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
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
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Research Article

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

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Figure 6

S. salivarius reduced arthritis severity in CIA mice.

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S. salivarius reduced arthritis severity in CIA mice.
(A) Schematic dia...
(A) Schematic diagram of experimental design for a preventive regimen with a collagen-induced arthritis (CIA) mouse model. (B) Clinical arthritis scores of CIA mice with or without S. salivarius K12 (1 × 108 CFU/mice) inoculation. K12 strains represent distinct inoculation methods. Specifically, K12-O denotes K12 inoculated intraorally, while K12-N indicates K12 inoculated intranasally. K12-N+O indicates K12 inoculated both intraorally and intranasally. Vehicle, n = 26; K12-O, n = 25; K12-N, n = 30; K12-N+O, n = 30. (C) Representative images of micro-CT of the paws in the indicated groups. Scale bars: 250 mm (top), 200 μm (bottom). (D) Representative images of H&E-stained sections and histopathological scoring of the paws in the indicated groups. n = 8 per group. (E) Schematic diagram of experimental design for a therapeutic regimen with a CIA mouse model. (F) Clinical arthritis scores in CIA mice with or without S. salivarius K12 inoculation. Vehicle, n = 37; K12-N+O, n = 29; K12-2(N+O), n = 19. K12-1 and K12-2 represent different colonization amounts of S. salivarius K12. Specifically, K12-1 and K12-2 indicate 1 × 108 CFU and 2 × 108 CFU of S. salivarius K12 for each mouse, respectively. (G) H&E-stained evaluation of the paws in the indicated groups. Vehicle, n = 16; K12-N+O, n = 8; K12-2(N+O), n = 8. Data were pooled from 2 (D and G) or 3 (B and F) independent experiments and are expressed as mean ± SEM. Significance was determined using 2-way ANOVA followed by Tukey’s multiple comparisons test (B and F) or 1-way ANOVA with Dunnett’s multiple comparisons test (D and G). *P < 0.05, **P < 0.01.

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