Corporal Michael J. Crescenz VAMC, Philadelphia, Pennsylvania, USA; Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Corporal Michael J. Crescenz VAMC, Philadelphia, Pennsylvania, USA; Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Invest Dermatol. 2021 Sep;141(9):2151-2160. doi: 10.1016/j.jid.2021.02.748. Epub 2021 Mar 22.
Dermatomyositis (DM) is a rare, systemic autoimmune disease that most frequently affects the skin, muscles, and lungs. The inflammatory infiltrate in the skin has not been fully characterized, and, in this study, we took a single-cell, unbiased approach using imaging mass cytometry. Substantial monocyte‒macrophage diversity was observed, with the CD14+ population correlating positively with Cutaneous Dermatomyositis Disease Area and Severity Index 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 Cutaneous Dermatomyositis Disease Area and Severity Index scores (P = 0.0268). IFN-β protein was highly upregulated in the T-cell, macrophage, dendritic cell, and endothelial cell populations of DM skin. Myeloid dendritic cells expressed phosphorylated peroxisome proliferator‒activated receptor γ, phosphorylated IRF3, IL-4, and IL-31, and their quantity correlated with itch as measured in Skindex-29. Plasmacytoid dendritic cells colocalized with IFN-γ in addition to the known colocalization with IFN-β. Nuclear phosphorylated peroxisome proliferator‒activated receptor γ expression was found in the DM endothelium. Imaging mass cytometry 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.
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。皮肤中的炎症浸润尚未得到充分描述，在这项研究中，我们采用了单细胞、无偏倚的方法，使用成像质谱细胞术。观察到大量单核细胞-巨噬细胞多样性，CD14+ 群体与皮肤肌炎疾病面积和严重程度指数评分呈正相关（P=0.031）。T 细胞区室显示 CD4+T、CD8+T 和 FOXP3+T 细胞。循环记忆 T 细胞的活化（CD69+）与皮肤肌炎疾病面积和严重程度指数评分呈正相关（P=0.0268）。IFN-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体中高度上调。髓样树突状细胞表达磷酸化过氧化物酶体增殖物激活受体 γ、磷酸化 IRF3、IL-4 和 IL-31，其数量与 Skindex-29 中测量的瘙痒相关。浆细胞样树突状细胞除了与 IFN-β 已知的共定位外，还与 IFN-γ 共定位。DM 内皮细胞中存在核磷酸化过氧化物酶体增殖物激活受体 γ 表达。成像质谱细胞术使我们能够对免疫细胞群体中的单细胞进行特征描述，并鉴定出 DM 中上调的细胞因子和炎症途径。这些发现对未来 DM 的靶向治疗发展具有重要意义。
