滤泡调节性T细胞（TFR）是位于生发中心（GC）的Treg细胞亚群，专门调控GC应答而维持体液免疫耐受。决定TFR系别稳定和功能的因素未知。Blimp1是T细胞重要转录因子，TFR表达Blimp1，但Blimp1在TFR中的功能未知。我们前期研究结果证实Blimp1是TFR系别稳定和功能所必须：Foxp3+Treg条件敲除Blimp1小鼠，TFR的Foxp3下调并分泌细胞因子，产生自身抗体。转录组和功能实验表明上调IL-23R很可能是Blimp1 KO TFR的系别不稳和功能下降的关键。拟进一步研究：1. IL-23R-pSTAT3信号在Blimp1 KO TFR上述异常中的作用；2. Blimp1抑制Treg/TFR IL-23R表达的机制； 3. Blimp1 KO TFR对GC扩增的贡献及在狼疮鼠模型中的作用。上述研究为阐明Blimp1调控TFR的系别稳定和功能提供理论基础。

Follicular regulatory T (TFR) cells are a specialized suppressive subset that control the germinal center (GC) response and maintain humoral self-tolerance. The mechanisms that maintain TFR lineage identity and suppressive activity remain largely unknown. Blimp1 is a master transcription factor to regulate T cells. TFR express Blimp1, however, the roles of Blimp1 in TFR still remain largely unknown. We observed that expression of Blimp1 by Foxp3+ TFR cells was essential for control of TFR lineage stability. Deletion of Blimp1 in Foxp3+ TFR cells resulted in defective TFR that expressed reduced levels of Foxp3, production of inflammatory cytokines resulting in production of autoantibodies. Transcriptome and function assay found that IL-23R upregulation might be the key for instability of Blimp1 KO TFR and decreased function. We will further observe: 1. The role of IL-23R-STAT3 signal pathway in the abnormal of Blimp1 KO TFR; 2. To determine how Blimp1 regulate the IL-23R expression by Treg/TFR; 3. Blimp1 KO TFR’s contribution in enhanced GC response in Foxp3 conditional Blimp1 knock out mice, and the role in SLE mouse model. The above studies suggest that expression of Blimp1 in TFR is essential for differentiation into functional TFR and stability of the TFR phenotype.