Table_1_In the skin lesions of patients with mycosis fungoides, the number of MRGPRX2-expressing cells is increased and correlates with mast cell numbers.docx

BackgroundMycosis fungoides (MF) is an indolent T-cell lymphoma that mainly affects the skin and presents with itch in more than half of the patients. Recently, the expression of Mas-related G protein-coupled receptor X2 (MRGPRX2), a receptor of mast cell (MC) responsible for the IgE-independent non-histaminergic itch, has been shown in lesional skin of patients with pruritic skin diseases, including chronic urticaria, prurigo, and mastocytosis. As of yet, limited knowledge exists regarding the MRGPRX2 expression in the skin of patients with MF.
ObjectivesTo investigate the number of MRGPRX2-expressing (MRGPRX2+) cells in the skin of patients with MF and its correlation with clinical and laboratory characteristics of the disease.
MethodsMRGPRX2 was analyzed in lesional and non-lesional skin of MF patients and healthy skin tissues by immunohistochemistry. Co-localization of MRGPRX2 with the MC marker tryptase was assessed by immunofluorescence. Public single-cell RNAseq data was reanalyzed to identify the MRGPRX2 expression on the distinct cell types.
ResultsIn lesional skin of MF patients, MRGPRX2+ cell number was higher than in non-lesional skin and healthy control skin (mean:15.12 vs. 6.84 vs. 5.51 cells/mm2, p=0.04), and correlated with MC numbers (r=0.73, p=0.02). MC was the primary cell type expressing MRGPRX2 in MF patients. The ratio of MRGPRX2+ MCs to MRGPRX2+ cells in lesional and non-lesional skin correlated with the severity of disease (r=0.71, p=0.02 and r=0.67, p=0.03, respectively).
ConclusionsOur findings point to the role of MRGPRX2 and MC in the pathogenesis of MF that should be investigated in further studies.

【背景】蕈样肉芽肿（Mycosis fungoides, MF）是一种惰性T细胞淋巴瘤，主要累及皮肤，超过半数患者会出现瘙痒症状。近期研究显示，Mas相关G蛋白偶联受体X2（Mas-related G protein-coupled receptor X2, MRGPRX2）——一种介导不依赖免疫球蛋白E（IgE）的非组胺能瘙痒的肥大细胞（mast cell, MC）受体——在慢性荨麻疹、痒疹、肥大细胞增生症等瘙痒性皮肤病患者的皮损皮肤中均有表达。截至目前，关于MF患者皮肤中MRGPRX2的表达情况，相关研究仍较为匮乏。

【目的】本研究旨在探究MF患者皮肤中表达MRGPRX2（MRGPRX2+）的细胞数量，及其与该疾病临床及实验室特征的相关性。

【方法】采用免疫组织化学法，对MF患者的皮损皮肤、非皮损皮肤以及健康皮肤组织中的MRGPRX2进行检测；通过免疫荧光法评估MRGPRX2与肥大细胞标志物类胰蛋白酶的共定位情况；重新分析公共单细胞RNA测序数据，以明确MRGPRX2在不同细胞类型中的表达特征。

【结果】MF患者皮损皮肤中的MRGPRX2+细胞数量显著高于非皮损皮肤与健康对照皮肤（平均值分别为15.12、6.84、5.51个细胞/mm²，p=0.04），且与肥大细胞数量呈正相关（r=0.73，p=0.02）。肥大细胞是MF患者中表达MRGPRX2的主要细胞类型。皮损皮肤与非皮损皮肤中，MRGPRX2+肥大细胞占MRGPRX2+细胞的比例均与疾病严重程度呈正相关（分别为r=0.71，p=0.02；r=0.67，p=0.03）。

【结论】本研究结果提示MRGPRX2与肥大细胞可能参与MF的发病过程，该结论有待后续研究进一步验证。