Single-Cell Sequencing of Immune Cell Heterogeneity in IgG4-Related Disease

作者：Xunyao Wu, Yu Peng, Jieqiong Li, Panpan Zhang, Zheng Liu, Hui Lu, Linyi Peng, Jiaxin Zhou, Yunyun Fei, Xiaofeng Zeng, Yan Zhao, Wen Zhang · 发表于：Frontiers in Immunology · 年份：2022 · DOI：10.3389/fimmu.2022.904288 · 被引用次数：29 · 研究领域：IgG4-Related and Inflammatory Diseases、Immunodeficiency and Autoimmune Disorders、Otitis Media and Relapsing Polychondritis

Background The IgG4-related disease (IgG4-RD) is an immune-mediated disorder with fibrotic manifestations. However, the transcriptional profiles of immune cell subsets at single-cell level are unknown. Herein, single-cell sequencing was used to assess the specific cell subpopulations and pathways in peripheral blood mononuclear cells (PBMCs) of IgG4-RD. Methods Single-cell sequencing was performed using the PBMCs from four patients with IgG4-RD and three healthy controls (HCs). Functional enrichment and cell analysis were performed through re-clustering of PBMCs to assess functional pathways and intercellular communication networks in IgG4-RD. Western blot and flow cytometry were used to verify sequencing and functional enrichment results. Results Four major cell types and 21 subtypes were identified. Further subclustering demonstrated that plasma B-cell proportions increased with increasing glycolysis/gluconeogenesis activity in IgG4-RD. Re-clustering of myeloid cells showed that EGR1 and CD36 expressions were significantly increased in CD14 + monocytes of IgG4-RD, as validated by Western blot analysis. Moreover, tumor necrosis factor (TNF) production pathways were positively regulated in CD14 + monocytes of IgG4-RD. In vitro stimulation showed that CD14 + monocytes of IgG4-RD could secrete higher levels of TNF-α . Notably, the proportions of CD8 central memory T (TCM) and TIGIT + CD8 cytotoxic T (CTL) increased in patients with IgG4-RD compared with HCs. Further interaction...