Mendeley出力
＜学術雑誌論文＞
Distinct disease-specific Tfh cell populations in 2 different fibrotic diseases: IgG_4-related disease and Kimura disease
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| 概要 | 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_4 (IgG_4-related disease, IgG_4-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_4-RD. Results: Infiltrating Tfh cells in tertiary lymphoid organs from IgG_4-RD were divided into 6 main clusters. We encountered abundant infiltrating IL-10–expressing LAG3^+ Tfh cells in patients with IgG_4-RD. Furthermore, we found that infiltrating AICDA^+CD19^+ B cells expressing IL-4, IL-10, and IL-21 receptors correlated with IgG4 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_4-RD, despite high serum levels of IgE (but low IgE in the disease lesions). Cytotoxic T cells were abundant in IgG_4-RD; in contrast, type 2 immune cells were abundant in KD. Conclusions: Our analysis revealed a novel subset of IL-10^+LAG3^+ Tfh cells infiltrating the affected organs of IgG_4-RD patients. In contrast, IL-13^+ Tfh cells and type 2 immune cells infiltrated those of KD patients.続きを見る |
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| 登録日 | 2024.04.04 |
| 更新日 | 2024.04.17 |