Highly Multiplexed Mass Cytometry Identifies the Immunophenotype in the Skin of Dermatomyositis.

Highly Multiplexed Mass Cytometry Identifies the Immunophenotype in the Skin of Dermatomyositis.
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高度复合质谱仪鉴定皮肌炎皮肤的免疫表型。

DOI:
10.1016/j.jid.2021.02.748
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发表时间:
2021-09
期刊:
The Journal of investigative dermatology
影响因子:
--
通讯作者:
Werth VP
Werth VP
中科院分区:
其他
文献类型:
--
作者:
Patel J;Maddukuri S;Li Y;Bax C;Werth VP

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皮肌炎(DM)是一种罕见的全身性自身免疫性疾病,最常影响皮肤、肌肉和肺部。皮肤中的炎性浸润物尚未完全确定,在这项研究中,我们采用了一种单细胞、无偏倚的成像质量细胞术(IMC)方法。观察到大量的单核巨噬细胞多样性,CD14+细胞群与皮肤皮肌炎疾病面积和严重程度指数评分呈正相关(p=0.031)。T细胞亚群包括CD4+T细胞、CD8+T细胞和FOXP3+T细胞。活化的(CD69+)循环记忆T细胞与CDASI评分呈正相关(p=0.0268)。干扰素β蛋白在DM皮肤的T细胞、巨噬细胞、树突状细胞和内皮细胞群中高度上调。髓系树突状细胞(MDCs)表达pPPARγ、pIRF3、IL4和IL31,并根据SKINDEX-29测定其数量与瘙痒程度相关。血浆细胞样树突状细胞(PDC)除了与干扰素γ共定位外,还与干扰素β共定位。糖尿病大鼠血管内皮细胞有核型pPPARγ表达。IMC使我们能够确定免疫细胞群中单个细胞的特征,并识别DM中上调的细胞因子和炎症途径。这些发现对未来糖尿病靶向治疗的发展具有重要的意义。
Dermatomyositis (DM) is a rare, systemic autoimmune disease that most frequently affects the skin, muscles, and lungs. The inflammatory infiltrate in skin has not been fully characterized and in this study we took an single cell, unbiased approach by using Imaging mass cytometry (IMC). Substantial monocyte-macrophage diversity was observed with the CD14+ population correlated positively with cutaneous dermatomyositis disease area and severity index (CDASI) scores (p=0.031). The T cell compartment revealed CD4+ T, CD8+ T, and FOXP3+ T cells. Activated (CD69+) circulating memory T cells correlated positively with CDASI scores (p=0.0268). IFNβ protein was highly upregulated in the T cell, macrophage, dendritic cell, and endothelial cell populations of DM skin. Myeloid DCs (mDCs) expressed pPPARγ, pIRF3, IL4, and IL31 and their quantity correlated with itch as measured in the Skindex-29. Plasmacytoid DCs (pDCs) colocalized with IFNγ in addition to the known colocalization with IFNβ. Nuclear pPPARγ expression was found in the DM endothelium. IMC allows us to characterize single cells in the immune cell population and identify upregulated cytokines and inflammatory pathways in DM. These findings have important implications for the development of future targeted therapies for DM.
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