两种不同纤维化疾病（IgG 相关疾病和 Kimura 病）中存在具有独特疾病特征的滤泡辅助性 T 细胞群体。
Distinct disease-specific Tfh cell populations in 2 different fibrotic diseases: IgG-related disease and Kimura disease.
机构信息
Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan; Dento-craniofacial Development and Regeneration Research Center, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
出版信息
J Allergy Clin Immunol. 2022 Aug;150(2):440-455.e17. doi: 10.1016/j.jaci.2022.03.034. Epub 2022 May 11.
BACKGROUND
How T follicular (Tfh) cells contribute to many different B-cell class-switching events during T-cell-dependent immune responses has been unclear. Diseases with polarized isotype switching offer a unique opportunity for the exploration of Tfh subsets. Secondary and tertiary lymphoid organs in patients with elevated tissue expression levels of IgE (Kimura disease, KD) and those of IgG (IgG-related disease, IgG-RD) can provide important insights regarding cytokine expression by Tfh cells.
OBJECTIVE
We sought to identify disease-specific Tfh cell subsets in secondary and tertiary lymphoid organs expressing IL-10 or IL-13 and thus identify different cellular drivers of class switching in 2 distinct types of fibrotic disorders: allergic fibrosis (driven by type 2 immune cells) and inflammatory fibrosis (driven by cytotoxic T lymphocytes).
METHODS
Single-cell RNA sequencing, in situ sequencing, and multicolor immunofluorescence analysis were used to investigate B cells, Tfh cells, and infiltrating type 2 cells in lesion tissues from patients with KD or IgG-RD.
RESULTS
Infiltrating Tfh cells in tertiary lymphoid organs from IgG-RD were divided into 6 main clusters. We encountered abundant infiltrating IL-10-expressing LAG3 Tfh cells in patients with IgG-RD. Furthermore, we found that infiltrating AICDACD19 B cells expressing IL-4, IL-10, and IL-21 receptors correlated with IgG expression. In contrast, we found that infiltrating IL-13-expressing Tfh cells were abundant in affected tissues from patients with KD. Moreover, we observed few infiltrating IL-13-expressing Tfh cells in tissues from patients with IgG-RD, despite high serum levels of IgE (but low IgE in the disease lesions). Cytotoxic T cells were abundant in IgG-RD; in contrast, type 2 immune cells were abundant in KD.
CONCLUSIONS
Our analysis revealed a novel subset of IL-10LAG3 Tfh cells infiltrating the affected organs of IgG-RD patients. In contrast, IL-13 Tfh cells and type 2 immune cells infiltrated those of KD patients.
背景
滤泡辅助性 T 细胞（Tfh）如何在 T 细胞依赖性免疫应答中促进多种不同的 B 细胞类别转换尚不清楚。具有极化同种型转换的疾病为探索 Tfh 亚群提供了独特的机会。在 IgE 组织表达水平升高的患者（Kimura 病，KD）和 IgG 相关疾病（IgG-RD）的次级和三级淋巴器官中，可以提供关于 Tfh 细胞细胞因子表达的重要见解。
目的
我们试图鉴定在次级和三级淋巴器官中表达 IL-10 或 IL-13 的疾病特异性 Tfh 细胞亚群，从而鉴定两种不同纤维化疾病（由 2 型免疫细胞驱动的过敏纤维化和由细胞毒性 T 淋巴细胞驱动的炎症纤维化）中不同的类别转换的细胞驱动因素。
方法
使用单细胞 RNA 测序、原位测序和多色免疫荧光分析来研究 KD 或 IgG-RD 患者病变组织中的 B 细胞、Tfh 细胞和浸润 2 型细胞。
结果
在 IgG-RD 的三级淋巴器官中浸润的 Tfh 细胞分为 6 个主要簇。我们在 IgG-RD 患者中发现了丰富的浸润性表达 IL-10 的 LAG3 Tfh 细胞。此外，我们发现表达 IL-4、IL-10 和 IL-21 受体的浸润性 AICDACD19 B 细胞与 IgG 表达相关。相比之下，我们发现 KD 患者病变组织中存在丰富的浸润性表达 IL-13 的 Tfh 细胞。此外，尽管 IgG-RD 患者血清 IgE 水平较高（但疾病病灶中 IgE 水平较低），但我们在 IgG-RD 患者的组织中发现浸润性表达 IL-13 的 Tfh 细胞很少。在 IgG-RD 中存在丰富的细胞毒性 T 细胞；相比之下，在 KD 中存在丰富的 2 型免疫细胞。
结论
我们的分析揭示了一种新型的浸润 IgG-RD 患者受累器官的 IL-10LAG3 Tfh 细胞亚群。相比之下，IL-13 Tfh 细胞和 2 型免疫细胞浸润了 KD 患者的病变组织。
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