Periodontitis is one of the most common human inflammatory diseases, yet the mechanisms that drive immunopathology and could be therapeutically targeted are not well defined. Here, we demonstrate an expansion of resident memory T helper 17 (T_H17) cells in human periodontitis. Phenocopying humans, T_H17 cells expanded in murine experimental periodontitis through local proliferation. Unlike homeostatic oral T_H17 cells, which accumulate in a commensal-independent and interleukin-6 (IL-6)–dependent manner, periodontitis-associated expansion of T_H17 cells was dependent on the local dysbiotic microbiome and required both IL-6 and IL-23. T_H17 cells and associated neutrophil accumulation were necessary for inflammatory tissue destruction in experimental periodontitis. Genetic or pharmacological inhibition of T_H17 cell differentiation conferred protection from immunopathology. Studies in a unique patient population with a genetic defect in T_H17 cell differentiation established human relevance for our murine experimental studies. In the oral cavity, human T_H17 cell defects were associated with diminished periodontal inflammation and bone loss, despite increased prevalence of recurrent oral fungal infections. Our study highlights distinct functions of T_H17 cells in oral immunity and inflammation and paves the way to a new targeted therapeutic approach for the treatment of periodontitis.

牙周炎是人类最常见的炎性疾病之一，但尚未明确定义驱动免疫病理学且可靶向治疗的机制。在这里，我们证明了人类牙周炎中常驻记忆T辅助17（T _H 17）细胞的扩展。进行人类复制的T _H 17细胞通过局部增殖在鼠实验性牙周炎中扩增。不同于稳态口腔内的T _H 17细胞，其以共生依赖性和白介素6（IL-6）依赖的方式积累，与牙周炎相关的T _H 17细胞的扩增取决于局部的致病菌微生物组，并且都需要IL-6和IL-23。Ť _{^ h}实验性牙周炎中炎性组织的破坏需要17个细胞和相关的嗜中性粒细胞积累。T _H 17细胞分化的遗传或药理抑制作用赋予了免疫病理学保护。在T _H 17细胞分化中存在遗传缺陷的独特患者群体中的研究建立了与我们的鼠类实验研究相关的人类相关性。在口腔中，尽管复发性口腔真菌感染的患病率增加，但人类T _H 17细胞缺陷与牙周炎症和骨质流失减少有关。我们的研究突出了T _H的独特功能口腔免疫和炎症中的17种细胞为治疗牙周炎的新型靶向治疗方法铺平了道路。