口腔扁平苔藓中环粘膜相关不变 T 细胞和 γδT 细胞的特征和功能。

Characterization and function of circulating mucosal-associated invariant T cells and γδT cells in oral lichen planus.

机构信息

The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

Department of Oral Medicine, School and Hospital of Stomatology, Wuhan University, Wuhan, China.

出版信息

J Oral Pathol Med. 2022 Jan;51(1):74-85. doi: 10.1111/jop.13250. Epub 2021 Oct 27.

DOI:10.1111/jop.13250

PMID:34637577

Abstract

BACKGROUND

Oral lichen planus (OLP) is a T-cell-mediated chronic inflammatory disease with uncertain aetiology. Mucosal-associated invariant T (MAIT) cells and γδT cells are unconventional, innate-like T cells with immunoregulatory capacity. This study aimed to investigate the potential effects of MAIT and γδT cells on the pathogenesis of OLP.

METHODS

Circulating MAIT cells and γδT cells were identified using flow cytometry. Surface proteins including CD4, CD8, CD69, CD103, CD49d, programmed death-1 (PD-1) and its ligand PD-L1 were assessed. Cytokines containing interleukin (IL)-4, IL-17, interferon (IFN)-γ, granzyme B and tumour necrosis factor (TNF)-α released by MAIT and γδT cells were measured following PMA and ionomycin stimulation.

RESULTS

Circulating MAIT and γδT cells were deficient in OLP. The percentage of CD4 , CD69 , CD103 and PD-1 MAIT cells was increased in OLP, while that of CD8 and CD49d MAIT cells was decreased. The percentage of CD103 , PD-1 and PD-L1 γδT cells was upregulated in OLP. Both the MAIT and γδT cells in OLP produced less IL-4 than controls. The granzyme B-producing MAIT cells were increased, while γδT cells secreting granzyme B and TNF-α were reduced in OLP. IL-17 and IFN-γ in OLP MAIT and γδT cells were not significantly different from that in controls. The frequency of OLP MAIT cells and the MAIT/γδT rate were positively associated with the disease severity.

CONCLUSION

The deficient MAIT and γδT cells expressing functional proteins and releasing cytokines may play an immunoregulatory role in the pathogenesis of OLP.

摘要

背景

口腔扁平苔藓（OLP）是一种以 T 细胞介导、病因不明的慢性炎症性疾病。黏膜相关不变 T（MAIT）细胞和 γδT 细胞是具有免疫调节能力的非传统先天样 T 细胞。本研究旨在探讨 MAIT 和 γδT 细胞对 OLP 发病机制的潜在影响。

方法

采用流式细胞术鉴定循环 MAIT 细胞和 γδT 细胞。评估表面蛋白包括 CD4、CD8、CD69、CD103、CD49d、程序性死亡受体-1（PD-1）及其配体 PD-L1。经 PMA 和离子霉素刺激后，测量 MAIT 和 γδT 细胞释放的细胞因子，包括白细胞介素（IL）-4、IL-17、干扰素（IFN）-γ、颗粒酶 B 和肿瘤坏死因子（TNF）-α。

结果

OLP 患者循环 MAIT 和 γδT 细胞数量减少。OLP 患者 MAIT 细胞中 CD4、CD69、CD103 和 PD-1 的比例增加，而 CD8 和 CD49d 的比例减少。OLP 患者 γδT 细胞中 CD103、PD-1 和 PD-L1 的比例上调。与对照组相比，OLP 患者的 MAIT 和 γδT 细胞产生的 IL-4 较少。MAIT 细胞产生的颗粒酶 B 增加，而 OLP 患者分泌颗粒酶 B 和 TNF-α的 γδT 细胞减少。OLP MAIT 和 γδT 细胞中的 IL-17 和 IFN-γ与对照组无显著差异。OLP MAIT 细胞的频率和 MAIT/γδT 比率与疾病严重程度呈正相关。