Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Fukuoka, Japan.
Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Fukuoka, Japan; Dento-craniofacial Development and Regeneration Research Center, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
J Allergy Clin Immunol. 2024 Feb;153(2):513-520.e10. doi: 10.1016/j.jaci.2023.08.019. Epub 2023 Aug 29.
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 CD4CXCR5Bcl6 GC-Tfh cells in affected lesions from patients with IgG4-RD.
Infiltrating CD4CXCR5Bcl6 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 HLAGZMK cytotoxic Tfh cells infiltrating affected organs in patients with IgG4-RD, suggesting that infiltrating Tfr cells might suppress cytotoxic Tfh cells.
生发中心（GC）反应受滤泡辅助性 T 细胞（Tfh）和滤泡调节性 T 细胞（Tfr）的调控，对于产生高亲和力抗体至关重要。组织释放抗原的获得性免疫反应可能主要在含有 GC 的三级淋巴器官（TLO）中诱导，这些 TLO 存在于受影响的组织中。IgG4 相关疾病（IgG4-RD）表现出极化的同种型转换和受影响组织中的 TLO。我们对这些 TLO 中的组织浸润性 T 细胞进行了单细胞转录组学分析，以全面、无偏地观察组织浸润性 GC-Tfh 细胞。
使用单细胞转录组学鉴定 IgG4-RD 患者 TLO 中的 GC-Tfh 细胞亚群。
使用单细胞 RNA 测序对分选的 CD3 T 细胞进行分析，并进行多色免疫荧光分析，以研究 IgG4-RD 患者病变中浸润的 CD4CXCR5Bcl6 GC-Tfh 细胞。
浸润性 CD4CXCR5Bcl6 Tfh 细胞被分为 5 个主要簇。我们在 IgG4-RD 患者中检测到具有细胞毒性相关特征的 HLA 颗粒酶 K（GZMK）Tfh 细胞。我们还观察到 IgG4-RD 患者中存在大量浸润性具有抑制相关特征的 Tfr 细胞。这些 GZMK Tfh 细胞和 Tfr 细胞在 IgG4-RD 患者的受影响组织中聚集在一起。
该单细胞数据集揭示了 IgG4-RD 患者受累器官浸润的一种新型 HLA-GZMK 细胞毒性 Tfh 细胞亚群，提示浸润性 Tfr 细胞可能抑制细胞毒性 Tfh 细胞。
