FAP‐α+ immunofibroblasts in oral lichen planus promote CD4+ T‐cell infiltration via CCL5 secretion

FAP‐α+ immunofibroblasts in oral lichen planus promote CD4+ T‐cell infiltration via CCL5 secretion
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DOI:
10.1111/exd.14613
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发表时间:
2022-05
影响因子:
3.6
通讯作者:
Yuyao Zhang;Ke-Zhong Liu;Juehua Cheng;Chenyu Zhou;Mengna Zhang;Yuan Fan
Yuyao Zhang;Ke-Zhong Liu;Juehua Cheng;Chenyu Zhou;Mengna Zhang;Yuan Fan
中科院分区:
医学2区
文献类型:
--
作者:
Yuyao Zhang;Ke-Zhong Liu;Juehua Cheng;Chenyu Zhou;Mengna Zhang;Yuan Fan

文献摘要

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口腔扁平苔藓(OLP)是一种T细胞介导的慢性炎症性疾病。CD 4 + T细胞浸润在OLP的发病机制中起着关键作用。成纤维细胞在病理条件下被激活并执行各种功能。本研究旨在探讨口腔扁平苔藓成纤维细胞对CD 4 + T细胞的免疫激活作用及其生物学功能。采用免疫组织化学方法检测成纤维细胞活化蛋白-α(FAP-α)在OLP患者和健康对照者口腔组织中的表达。此外,通过定量PCR、蛋白质印迹和酶联免疫吸附试验检测从OLP患者和健康对照者的口腔组织分离的成纤维细胞中FAP-α和C-C基序趋化因子配体5(CCL 5)的表达。此外,我们使用流式细胞术和Transwell测定评估了成纤维细胞对CD 4 + T细胞增殖、凋亡和迁移的影响。我们发现FAP-α在OLP患者口腔组织中的表达显著高于健康对照。FAP-α和CCL 5表达水平在OLP成纤维细胞中显著上调。此外,OLP成纤维细胞促进CD 4 + T细胞增殖和迁移,并抑制CD 4 + T细胞凋亡。总之,我们的研究结果表明,OLP成纤维细胞被免疫激活,并诱导OLP中的CD 4 + T细胞浸润。
Oral lichen planus (OLP) is a T cell–mediated, chronic inflammatory disease. CD4+ T‐cell infiltration plays a crucial role in the pathogenesis of OLP. Fibroblasts are activated under pathological conditions and perform various functions. This study was designed to explore the immune activation and biological functions of OLP fibroblasts on CD4+ T cells. We detected the expression of fibroblast activation protein‐alpha (FAP‐α) in the oral tissues of patients with OLP and healthy controls using immunohistochemistry. Furthermore, expression of FAP‐α and C‐C motif chemokine ligand 5 (CCL5) in fibroblasts isolated from oral tissues of patients with OLP and healthy controls was assayed by quantitative PCR, Western blotting and enzyme‐linked immunosorbent assay. Moreover, we assessed the effects of fibroblasts on CD4+ T‐cell proliferation, apoptosis and migration using flow cytometry and Transwell assays. We found that FAP‐α expression in the oral tissues of patients with OLP was significantly higher than that in healthy controls. FAP‐α and CCL5 expression levels were significantly upregulated in OLP fibroblasts. Moreover, OLP fibroblasts promoted CD4+ T‐cell proliferation and migration and inhibited CD4+ T cell apoptosis. In summary, our findings indicate that OLP fibroblasts are immunologically activated and induce CD4+ T‐cell infiltration in OLP.