类风湿关节炎(RA)是常见的系统性自身免疫病，是致残率最高的疾病之一，微生物是其发病的关键诱因。我们前期研究运用二代高通量测序分析技术，发现RA患者的扁桃体菌群明显失调，唾液链球菌及其细菌素的编码基因显著减少，并且唾液链球菌可通过下调滤泡辅助性T（Tfh）细胞而抑制实验性关节炎发生发展。作为唾液链球菌重要的效应分子，唾液链球菌素（salivaricin）在RA发病中对Tfh细胞的作用机制有待深入探讨。因此，本项目拟进一步开展以下研究：1）唾液链球菌素对RA患者外周血以及实验性关节炎中Tfh细胞亚群的作用；2）唾液链球菌素调控Tfh的关键分子及信号通路。本课题将首次研究唾液链球菌素对Tfh细胞亚群的调节作用，具有原创性。同时，本项目是一项基础与临床相结合的研究，为RA早期诊断及免疫治疗提供了重要靶点，既有科学意义，又有临床应用价值。

Rheumatic arthritis (RA) is a common systemic autoimmunity disease with high disability rate, and microorganism is the primary trigger initiating RA. Our preliminary research using next-gene sequencing found for the first time that the RA tonsillar microbiota was dysbiosis, and Streptococcus salivarius as well as the derived bacteriocin salivaricin was significantly reduced. Furthermore, we demonstrated that S. salivarius could inhibit the initiation and development of experimental arthritis through down-regulating of T follicular helper (Tfh) cells. Being the key effector of S. salivarius, the mechanism of salivaricin in regulating Tfh cells in RA remained to be illustrated. Therefore, the proposed study aimed to investigate: 1) the immunological effects of salivaricin on Tfh cells from RA patients and experimental arthritis models; 2) the key moleculars and signaling pathways of salivaricin in regulating Tfh cells. The project will provide the primary source for the immunoregulatory activity of salivaricin on Tfh cells. Further, the study will offer a significant documentation for the clinical applications of salivaricin in the monitoring and immunotherapy of RA.