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.