Fusobacterium nucleatum aggravates rheumatoid arthritis through FadA-containing outer membrane vesicles
Fusobacterium nucleatum aggravates rheumatoid arthritis through FadA-containing outer membrane vesicles
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DOI：
10.1016/j.chom.2023.03.018
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发表时间：
2023-05-10
影响因子：
30.3
通讯作者：
Li, Juan
中科院分区：
文献类型：
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作者：
Hong, Mukeng;Li, Zhuang;Li, Juan
Rheumatoid arthritis (RA) is an autoimmune disorder that has been associated with the gut microbiota. However, whether and how the gut microbiota plays a pathogenic role in RA remains unexplored. Here, we observed that Fusobacterium nucleatum is enriched in RA patients and positively associated with RA severity. F. nucleatum similarly aggravates arthritis in a mouse model of collagen-induced arthritis (CIA). F. nucleatum outer membrane vesicles (OMVs) containing the virulence determinant FadA translo-cate into the joints, triggering local inflammatory responses. Specifically, FadA acts on synovial macro-phages, resulting in the activation of the Rab5a GTPase involved in vesicle trafficking and inflammatory pathways and YB-1, a key regulator of inflammatory mediators. OMVs containing FadA and heightened Rab5a-YB-1 expression were observed in RA patients compared with controls. These findings suggest a causal role of F. nucleatum in aggravating RA and provide promising therapeutic targets for clinically ameliorating RA.
