JID-2023-1028.R2 - Imaging Mass Cytometry in Psoriatic Disease reveals immune profile heterogeneity in skin and synovial tissue

Imaging Mass Cytometry (IMC) is a technology that enables comprehensive analysis of cellular phenotypes at the tissue level. We performed a multi-parameter characterization of structural and immune cell populations in psoriatic skin and synovial tissue samples aimed at characterizing immune cell differences in patients with psoriasis, psoriatic arthritis (PsA). A panel of 33 antibodies was used to stain selected immune and structural cell populations. IMC data were segmented into single cells based on combinations of antibody stains. Single cells were then clustered into cell categories based on pre-specified markers. The spatial relationships of different cell populations were assessed using neighborhood analysis. Among all cell types in the skin and synovium, lymphoid cells accounted for the most prevalent cell type. T cells and macrophages were the most prevalent immune cell type in the synovium and B cells and NK cells were also identified. Neighborhood analysis showed high correlation between synovial T cells, B cells, macrophages, dendritic cells and neutrophils suggesting spatial organization. Innate and adaptive immune cells can be reliably identified using IMC in skin and synovium. Inter-patient heterogeneity exists in tissue cell populations. IMC provides opportunities for exploring in depth underlying immunological mechanisms driving psoriasis and PsA.成像质谱流式细胞术（Imaging Mass Cytometry，IMC）是一种可在组织层面实现细胞表型全面分析的技术。本研究对银屑病皮肤及滑膜组织样本中的结构细胞与免疫细胞群开展多参数表征，旨在解析银屑病与银屑病关节炎（psoriatic arthritis，PsA）患者体内的免疫细胞差异。研究采用包含33种抗体的抗体组合对目标免疫细胞与结构细胞群进行染色标记。成像质谱流式细胞术数据依据抗体染色组合被分割为单细胞数据，随后基于预先设定的标志物将单细胞聚类为不同细胞类群。研究通过邻域分析方法评估了不同细胞群的空间关联关系。在皮肤与滑膜的所有细胞类型中，淋巴细胞为占比最高的细胞类群。滑膜组织中占比最高的免疫细胞类群为T细胞与巨噬细胞，同时还鉴定出了B细胞与自然杀伤细胞（Natural Killer Cells）。邻域分析结果显示，滑膜组织中的T细胞、B细胞、巨噬细胞、树突状细胞与中性粒细胞之间存在高度相关性，提示其存在空间组织结构。借助成像质谱流式细胞术，可在皮肤与滑膜组织中可靠鉴定先天免疫细胞与适应性免疫细胞。不同患者的组织细胞群存在异质性。成像质谱流式细胞术为深入解析驱动银屑病及银屑病关节炎的潜在免疫机制提供了重要研究契机。