BCL6公司
生发中心
细胞毒性T细胞
颗粒酶
免疫学
生物
CXCR5型
B细胞
免疫系统
白细胞介素21
抗体
CD8型
化学
穿孔素
遗传学
体外
作者
Ryuichi Aoyagi,Takashi Maehara,Risako Koga,Ryusuke Munemura,Tadashi Tomonaga,Yasuki Murakami,Akira Doi,Hidetaka Yamamoto,Tamotsu Kiyoshima,Seiji Kawano,Seiji Nakamura
标识
DOI:10.1016/j.jaci.2023.08.019
摘要
Germinal center (GC) responses controlled by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells are crucial for the generation of high-affinity antibodies. Acquired immune responses to tissue-released antigens might be mainly induced in tertiary lymphoid organs (TLOs) with GCs in affected tissues. IgG4-related disease (IgG4-RD) demonstrates polarized isotype switching and TLOs in affected tissues. We performed single-cell transcriptomics of tissue-infiltrating T cells from these TLOs to obtain a comprehensive, unbiased view of tissue-infiltrating GC-Tfh cells.To identify GC-Tfh-cell subsets in TLOs in patients with IgG4-RD using single-cell transcriptomics.Single-cell RNA sequencing of sorted CD3+ T cells and multicolor immunofluorescence analysis were used to investigate CD4+CXCR5+Bcl6+ GC-Tfh cells in affected lesions from patients with IgG4-RD.Infiltrating CD4+CXCR5+Bcl6+ Tfh cells were divided into 5 main clusters. We detected HLA+ granzyme K+ (GZMK+) Tfh cells with cytotoxicity-associated features in patients with IgG4-RD. We also observed abundant infiltrating Tfr cells with suppressor-associated features in patients with IgG4-RD. These GZMK+ Tfh cells and Tfr cells clustered together in affected tissues from patients with IgG4-RD.This single-cell data set revealed a novel subset of HLA+GZMK+ cytotoxic Tfh cells infiltrating affected organs in patients with IgG4-RD, suggesting that infiltrating Tfr cells might suppress cytotoxic Tfh cells.
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