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未经控制的严重慢性鼻-鼻窦炎伴鼻息肉患者鼻窦黏膜的多组学单细胞图谱。

The multi-omics single-cell landscape of sinus mucosa in uncontrolled severe chronic rhinosinusitis with nasal polyps.

机构信息

The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Department of Otorhinolaryngology, International Airway Research Center, Guangzhou, China; Upper Airway Research Laboratory, Ghent University, Ghent, Belgium.

The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Department of Otorhinolaryngology, International Airway Research Center, Guangzhou, China; Upper Airway Research Laboratory, Ghent University, Ghent, Belgium; Department of Allergy, Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, PR China; Beijing key laboratory of nasal diseases, Beijing Institute of Otolaryngology, Beijing, PR China.

出版信息

Clin Immunol. 2023 Nov;256:109791. doi: 10.1016/j.clim.2023.109791. Epub 2023 Sep 26.

DOI:10.1016/j.clim.2023.109791
PMID:37769787
Abstract

Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with elevated levels of type 2 inflammatory cytokines and raised immunoglobulin concentrations in nasal polyp tissue. By using single-cell RNA sequencing, transcriptomics, surface proteomics, and T cell and B cell receptor sequencing, we found the predominant cell types in nasal polyps were shifted from epithelial and mesenchymal cells to inflammatory cells compared to nasal mucosa from healthy controls. Broad expansions of CD4 T effector memory cells, CD4 tissue-resident memory T cells, CD8 T effector memory cells and all subtypes of B cells in nasal polyp tissues. The T and B cell receptor repertoires were skewed in NP. This study highlights the deviated immune response and remodeling mechanisms that contribute to the pathogenesis of uncontrolled severe CRSwNP. CLINICAL IMPLICATIONS: We identified differences in the cellular compositions, transcriptomes, proteomes, and deviations in the immune profiles of T cell and B cell receptors as well as alterations in the intercellular communications in uncontrolled severe CRSwNP patients versus healthy controls, which might help to define potential therapeutic targets in the future.

摘要

未经控制的严重慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)与鼻息肉组织中 2 型炎症细胞因子水平升高和免疫球蛋白浓度升高有关。通过使用单细胞 RNA 测序、转录组学、表面蛋白质组学以及 T 细胞和 B 细胞受体测序,我们发现与健康对照组的鼻腔黏膜相比,鼻息肉中的主要细胞类型从上皮细胞和间充质细胞转变为炎症细胞。CD4 T 效应记忆细胞、CD4 组织驻留记忆 T 细胞、CD8 T 效应记忆细胞和所有 B 细胞亚型在鼻息肉组织中广泛扩增。T 细胞和 B 细胞受体库在 NP 中发生了偏倚。本研究强调了导致未经控制的严重 CRSwNP 发病机制的免疫反应和重塑机制的偏差。临床意义:我们确定了在细胞组成、转录组、蛋白质组以及 T 细胞和 B 细胞受体的免疫特征偏差以及细胞间通讯改变方面,与健康对照组相比,未经控制的严重 CRSwNP 患者存在差异,这可能有助于未来确定潜在的治疗靶点。

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