提吉特
流式细胞术
生物
细胞
T细胞
细胞分化
分子生物学
B细胞
免疫学
抗体
免疫系统
遗传学
基因
作者
Zongfei Ji,Weiqi Lu,Shuang Wu,Yong Zhang,Dan Meng,Xiao Zhang,Xiaojuan Dai,Huiyong Chen,Lili Ma,Yan Sun,Lindi Jiang,Xiaoni Kong
标识
DOI:10.3390/ijms241813735
摘要
Abnormal B cell differentiation plays a critical role in IgG4-related disease (IgG4-RD), but the underlying mechanism remains largely unknown. We investigated the cell landscape from three IgG4-RD retroperitoneal tissues and three control tissues using single-cell RNA-sequencing. Critical cell type or markers were further validated in the peripheral blood from the patients with IgG4-RD and healthy controls via flow cytometry as well as in the IgG4-RD and control tissue via immunofluorescence staining. The increases in B cells, plasma cells, and CD4+ T cells were found in IgG4-RD retroperitoneal tissue. Importantly, among CD4+ T cells, an increase in CD4+CXCR5-PD1hi peripheral T helper (Tph) cells with a high expression of IL-21 and TIGIT was discovered in IgG4-RD tissue, which was further validated in peripheral blood of the patients with IgG4-RD. The Tph cell and TIGIT+ Tph cell proportion were remarkably higher in active IgG4-RD patients and correlated with disease activity. Moreover, TIGIT+CD4+ cells were able to promote B cell differentiation via IL-21. Our study revealed that Tph cells are increased in IgG4-RD and probably play critical roles in B cell differentiation through TIGIT-IL-21 axis. Peripheral Tph cell and TIGIT+Tph cell are potential markers for IgG4-RD disease activity.
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