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

Xiaoyan Ye; Yachun Li; Bixing Fang; Yizhang Yuan; Danni Feng; Hexin Chen; Jian Li; Qingxiang Meng; Shaobing Xiong; Dongmei Ye; Linyi Jiao; Dehua Chen; Ruchong Chen; Wenbin Lei; Yifang Gao; Chunwei Li

doi:10.1016/j.jaci.2023.06.021

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

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

Authors

Xiaoyan Ye¹, Yachun Li², Bixing Fang², Yizhang Yuan², Danni Feng², Hexin Chen², Jian Li¹, Qingxiang Meng³, Shaobing Xiong², Dongmei Ye⁴, Linyi Jiao², Dehua Chen², Ruchong Chen⁵, Wenbin Lei², Yifang Gao⁶, Chunwei Li⁷

Affiliations

¹ 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.
² Department of Otolaryngology, Department of Allergy, Guangzhou Key Laboratory of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
³ Department of Otorhinolaryngology Head and Neck Surgery, Guangzhou First People's Hospital, Guangzhou, China.
⁴ Organ Transplantation Centre, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁵ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Department of Allergy and Clinical Immunology, Guangzhou Medical University, Guangzhou, China.
⁶ Organ Transplantation Centre, Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: gaoyf26@sysu.edu.cn.
⁷ Department of Otolaryngology, Department of Allergy, Guangzhou Key Laboratory of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: hi_chunwei@aliyun.com.

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

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.

Keywords: Mucosal-associated invariant T cells; chronic rhinosinusitis with nasal polyps; functional subsets; neutrophil.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chronic Disease
Cytokines
Humans
Inflammation / complications
Mucosal-Associated Invariant T Cells*
Nasal Polyps*
Rhinitis*
Sinusitis*

Substances

Cytokines