Oral γδT17 cells induced by macrophage-derived extracellular vesicles in periodontitis exacerbate rheumatoid arthritis

  • Cell Rep. 2026 Jun 23;45(6):117372. doi: 10.1016/j.celrep.2026.117372.
Wenzhe Wang  1 ,  Tingjie Liu  1 ,  Xinli Wang  2 ,  Zhiwei Dong  3 ,  Jianhua Yang  1 ,  Xiaoning He  1 ,  Jiahuan Dong  1 ,  Hanzhe Wang  1 ,  Yiming Wang  1 ,  Ruina Dong  1 ,  Tianhao Yuan  4 ,  Yan Jin  5 ,  Bei Li  6
Affiliations
  • 1. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China.
  • 2. Department of Orthopedics, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
  • 3. Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, China.
  • 4. Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
  • 5. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: [email protected].
  • 6. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. Electronic address: [email protected].
PMID: 42225070 DOI: 10.1016/j.celrep.2026.117372
Abstract

Periodontitis is one of the most common human inflammatory diseases, yet the immune mechanism linking oral and systemic immune responses is not well defined. Here, we show that the accumulation of interleukin-17 (IL-17)-producing γδT (γδT17) cells occurs not only in the gingiva and cervical lymph nodes (CLNs) but also in the peripheral lymph nodes and spleen of ligation-induced periodontitis (LIP) mice. Strikingly, oral γδT17 cells derived from LIP migrate to the inflamed joint and exacerbate rheumatoid arthritis (RA) in a collagen-induced arthritis mice model. Mechanistically, we demonstrate that dysbiosis in LIP increases the production of Complement Component 3 (C3)-enriched extracellular vesicles (EVs) derived from macrophages. These C3-enriched EVs are taken up by γδT cells and stimulate the intracellular C3a receptor to drive IL-17A production in γδT cells. Our findings reveal a previously unrecognized immunological mechanism linking periodontitis to RA through the accumulation and migration of oral γδT17 cells.

Keywords
C3; CP: immunology; extracellular vesicles; mucosal immunity; rheumatoid arthritis; γδT17 cells.
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