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17 型黏膜相关恒定 T 细胞有助于鼻息肉患者的中性粒细胞炎症。

Type 17 mucosal-associated invariant T cells contribute to neutrophilic inflammation in patients with nasal polyps.

机构信息

Department of Otolaryngology, Department of Allergy, Guangzhou Key Laboratory of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University, Nanning, China.

Department of Otolaryngology, Department of Allergy, Guangzhou Key Laboratory of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

J Allergy Clin Immunol. 2023 Nov;152(5):1153-1166.e12. doi: 10.1016/j.jaci.2023.06.021. Epub 2023 Jul 10.

DOI:10.1016/j.jaci.2023.06.021
PMID:37437744
Abstract

BACKGROUND

Immune regulation in chronic rhinosinusitis with nasal polyps (CRSwNP) with a neutrophilic endotype remains unclear. Mucosal-associated invariant T (MAIT) cells are tissue-resident innate T lymphocytes that respond quickly to pathogens and promote chronic mucosal inflammation.

OBJECTIVE

We aimed to investigate the roles of MAIT cells in neutrophilic CRSwNP.

METHODS

Nasal tissues were obtained from 113 patients with CRSwNP and 29 control subjects. Peripheral and tissue MAIT cells and their subsets were analyzed by flow cytometry. Polyp-derived MAIT cells were analyzed by RNA sequencing to study their effects on neutrophils.

RESULTS

Endotypes of CRSwNP were classified as paucigranulocytic (n = 21), eosinophilic (n = 29), neutrophilic (n = 39), and mixed granulocytic (n = 24). Frequencies of MAIT cells were significantly higher in neutrophilic (3.62%) and mixed granulocytic (3.60%) polyps than in control mucosa (1.78%). MAIT cell percentages positively correlated with local neutrophil counts. MAIT cells were more enriched in tissues than in matched PBMCs. The frequencies of MAIT1 subset or IFN-γ MAIT cells were comparable among control tissues and CRSwNP subtypes. The proportions of MAIT17 subset or IL-17A MAIT cells were significantly increased in neutrophilic or mixed granulocytic polyps compared with controls. RNA sequencing revealed type 17 and pro-neutrophil profiles in neutrophilic polyp-derived MAIT cells. In patients with neutrophilic CRSwNP, the proportions of MAIT and MAIT17 cells were positively correlated with local proinflammatory cytokines and symptom severity. In vitro experiments demonstrated that neutrophilic polyp-derived MAIT cells promoted neutrophil migration, survival, and activation.

CONCLUSIONS

MAIT cells from neutrophilic CRSwNP demonstrate type 17 functional properties and promote neutrophil infiltration in nasal mucosa.

摘要

背景

伴有中性粒细胞表型的慢性鼻-鼻窦炎(CRSwNP)的免疫调节仍不清楚。黏膜相关不变 T(MAIT)细胞是组织驻留的先天 T 淋巴细胞,对病原体反应迅速,并促进慢性黏膜炎症。

目的

我们旨在研究 MAIT 细胞在中性粒细胞性 CRSwNP 中的作用。

方法

从 113 例 CRSwNP 患者和 29 例对照者的鼻组织中获取标本。通过流式细胞术分析外周血和组织 MAIT 细胞及其亚群。通过 RNA 测序分析息肉衍生的 MAIT 细胞,以研究其对中性粒细胞的作用。

结果

CRSwNP 的表型分为少粒细胞型(n=21)、嗜酸性粒细胞型(n=29)、中性粒细胞型(n=39)和混合粒细胞型(n=24)。中性粒细胞型(3.62%)和混合粒细胞型(3.60%)息肉中的 MAIT 细胞频率明显高于对照黏膜(1.78%)。MAIT 细胞百分比与局部中性粒细胞计数呈正相关。MAIT 细胞在组织中的丰度高于其在匹配 PBMCs 中的丰度。MAIT1 亚群或 IFN-γ MAIT 细胞的频率在对照组织和 CRSwNP 亚型之间相似。中性粒细胞型或混合粒细胞型息肉中的 MAIT17 亚群或 IL-17A MAIT 细胞比例与对照组相比显著增加。RNA 测序显示中性粒细胞性息肉衍生的 MAIT 细胞具有 17 型和促中性粒细胞特征。在伴有中性粒细胞性 CRSwNP 的患者中,MAIT 和 MAIT17 细胞的比例与局部前炎症细胞因子和症状严重程度呈正相关。体外实验表明,中性粒细胞性息肉衍生的 MAIT 细胞促进中性粒细胞迁移、存活和激活。

结论

伴有中性粒细胞性 CRSwNP 的 MAIT 细胞表现出 17 型功能特性,并促进鼻黏膜中中性粒细胞的浸润。

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