Aberrant follicular regulatory T cells associate with immunoglobulin hyperproduction in nasal polyps with ectopic lymphoid tissues - 04/04/24

Doi : 10.1016/j.jaci.2023.11.913

Jia Song, MD, PhD ^a,^b,^{^{∗
These authors contributed equally to this work.}}, Hai Wang, MD, PhD ^a,^b,^{^{∗
These authors contributed equally to this work.}}, Zhe-Zheng Wang, MD, PhD ^a,^b,^{^{∗
These authors contributed equally to this work.}}, Cui-Lian Guo, MD, PhD ^a,^b, Wen-Xuan Xiang, MD ^a, Jing-Xian Li, MD, PhD ^a,^b, Zhi-Chao Wang, MD, PhD ^a,^b, Ji-Xin Zhong, MD, PhD ^c,^d, Kun Huang, PhD ^e, Robert P. Schleimer, PhD ^f, Yin Yao, MD, PhD ^a,^b,^d,^⁎ , Zheng Liu, MD, PhD ^a,^b,^d,^⁎
^a Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
^b Hubei Clinical Research Center for Nasal Inflammatory Diseases, Wuhan, China
^c Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
^d Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
^e Tongji School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
^f Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill

^∗Corresponding author: Zheng Liu, MD, PhD, Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, China.Department of Otolaryngology-Head and Neck SurgeryTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyNo. 1095 Jiefang AvenueWuhan430030China^∗Yin Yao, MD, PhD, Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, China.Department of Otolaryngology-Head and Neck SurgeryTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyNo. 1095 Jiefang AvenueWuhan430030China

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Abstract

Background

Ectopic lymphoid tissues (eLTs) and associated follicular helper T (T_FH) cells contribute to local immunoglobulin hyperproduction in nasal polyps (NPs). Follicular regulatory T (T_FR) cells in secondary lymphoid organs counteract T_FH cells and suppress immunoglobulin production; however, the presence and function of T_FR cells in eLTs in peripheral diseased tissues remain poorly understood.

Objective

We sought to investigate the presence, phenotype, and function of T_FR cells in NPs.

Methods

The presence, abundance, and phenotype of T_FR cells in NPs were examined using single-cell RNA sequencing, immunofluorescence staining, and flow cytometry. Sorted polyp and circulating T-cell subsets were cocultured with autologous circulating naïve B cells, and cytokine and immunoglobulin production were measured by ELISA.

Results

T_FR cells were primarily localized within eLTs in NPs. T_FR cell frequency and T_FR cell/T_FH cell ratio were decreased in NPs with eLTs compared with NPs without eLTs and control inferior turbinate tissues. T_FR cells displayed an overlapping phenotype with T_FH cells and FOXP3⁺ regulatory T cells in NPs. Polyp T_FR cells had reduced CTLA-4 expression and decreased capacity to inhibit T_FH cell–induced immunoglobulin production compared with their counterpart in blood and tonsils. Blocking CTLA-4 abolished the suppressive effect of T_FR cells. Lower vitamin D receptor expression was observed on polyp T_FR cells compared with T_FR cells in blood and tonsils. Vitamin D treatment upregulated CTLA-4 expression on polyp T_FR cells and restored their suppressive function in vitro.

Conclusions

Polyp T_FR cells in eLTs have decreased CLTA-4 and vitamin D receptor expression and impaired capacity to suppress T_FH cell–induced immunoglobulin production, which can be reversed by vitamin D treatment in vitro.

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Key words : Ectopic lymphoid tissue, follicular regulatory T cell, immunoglobulin, nasal polyps, vitamin D

Abbreviations used : AID, B_GC, CRSwNP, eLTs, GC, ICOS, IT, T_FH, T_FR, T_REG, VDR

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Vol 153 - N° 4

P. 1025-1039 - avril 2024 Retour au numéro

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Aberrant follicular regulatory T cells associate with immunoglobulin hyperproduction in nasal polyps with ectopic lymphoid tissues - 04/04/24

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