T follicular regulatory (Tfr) cells are a new subset of regulatory T (T reg) cells localized in the germinal center to limit the humoral response. Until now, the physiological function of Tfr cells has been largely unknown. In this study, we developed a Bcl6^fl/flFoxp3Cre mouse to analyze the function of Tfr cells in immune and autoimmune responses. These mice exhibited enhanced immunity to influenza virus; moreover, Bcl6^fl/flFoxp3Cre/Cre mice developed late-onset spontaneous autoimmune diseases, affecting the salivary glands with lymphocyte infiltration and antibody deposition. In a mouse experimental Sjögren’s syndrome model, ablation of Bcl6 in T reg cells greatly enhanced disease development. Conversely, Bcl6^fl/flCd4Cre mice were protected in the model. Thus, our study indicates that Tfr cells control autoimmune diseases and can be targeted in infectious and autoimmune disease.

T滤泡性调节（Tfr）细胞是位于生发中心以限制体液反应的调节性T（T reg）细胞的新子集。到目前为止，Tfr细胞的生理功能一直是未知的。在这项研究中，我们开发了Bcl6转录^{FL / FL} Foxp3Cre鼠标来分析Tfr中的细胞免疫和自身免疫反应的功能。这些小鼠对流感病毒表现出增强的免疫力。此外，Bcl6转录因子^{FL / FL} Foxp3Cre /酶Cre小鼠发展迟发性自发自身免疫性疾病，影响与淋巴细胞浸润和抗体沉积唾液腺。在小鼠实验性干燥综合征模型中，T reg细胞中Bcl6的消融极大地促进了疾病的发展。反过来，BCL6 ^{FL / FL} Cd4Cre小鼠模型中的保护。因此，我们的研究表明，Tfr细胞可控制自身免疫性疾病，并且可以靶向感染和自身免疫性疾病。