Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, PR China.
Department of Pathology, Qingdao Chengyang People's Hospital, Qingdao, PR China.
J Pathol. 2023 Sep;261(1):105-119. doi: 10.1002/path.6151. Epub 2023 Aug 7.
Granulomatous slack skin (GSS) is an extremely rare subtype of cutaneous T-cell lymphoma accompanied by an abundant number of macrophages and is clinically characterized by the development of pendulous skin folds. However, the characteristics of these macrophages in GSS remain unclear. Here, we conducted a spatial transcriptomic study on one frozen GSS sample and drew transcriptomic maps of GSS for the first time. Gene expression analysis revealed the enrichment of three clusters with macrophage transcripts, each exhibiting distinct characteristics suggesting that their primary composition consists of different subpopulations of macrophages. The CD163 /CD206 cluster showed a tumor-associated macrophage (TAM) M2-like phenotype and highly expressed ZFP36, CCL2, TNFAIP6, and KLF2, which are known to be involved in T-cell interaction and tumor progression. The APOC1 /APOE cluster presented a non-M1 or -M2 phenotype and may be related to lipid metabolism. The CD11c /LYZ cluster exhibited an M1-like phenotype. Notably, these cells strongly expressed MMP9, MMP12, CHI3L1, CHIT1, COL1A1, TIMP1, and SPP1, which are responsible for extracellular matrix (ECM) degradation and tissue remodeling. This may partially explain the symptoms of cutaneous relaxation in GSS. Further immunohistochemistry on four GSS cases demonstrated that CD11c predominantly marked granulomas and multinucleated giant cells, whereas CD163 was mainly expressed on scattered macrophages, appearing as a mutually exclusive pattern. The expression pattern of MMP9 overlapped with that of CD11c, implying that CD11c macrophages may be a source of MMP9. Our data shed light on the characteristics of macrophages in the GSS microenvironment and provide a theoretical basis for the application of MMP9 inhibitors to prevent cutaneous relaxation of GSS. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
肉芽肿性松弛皮肤（GSS）是一种极为罕见的皮肤 T 细胞淋巴瘤亚型，伴有大量巨噬细胞，临床上以悬垂皮肤褶皱的发展为特征。然而，GSS 中这些巨噬细胞的特征尚不清楚。在这里，我们对一个冷冻 GSS 样本进行了空间转录组学研究，首次绘制了 GSS 的转录组图谱。基因表达分析显示，有三个富含巨噬细胞转录物的簇被富集，每个簇都表现出不同的特征，表明它们的主要组成部分由不同的巨噬细胞亚群组成。CD163/CD206 簇表现出肿瘤相关巨噬细胞（TAM）M2 样表型，并高度表达 ZFP36、CCL2、TNFAIP6 和 KLF2，这些已知参与 T 细胞相互作用和肿瘤进展。APOC1/APOE 簇表现出非 M1 或 -M2 表型，可能与脂质代谢有关。CD11c/LYZ 簇表现出 M1 样表型。值得注意的是，这些细胞强烈表达 MMP9、MMP12、CHI3L1、CHIT1、COL1A1、TIMP1 和 SPP1，它们负责细胞外基质（ECM）降解和组织重塑。这可能部分解释了 GSS 中皮肤松弛的症状。对四个 GSS 病例的进一步免疫组织化学研究表明，CD11c 主要标记肉芽肿和多核巨细胞，而 CD163 主要表达在分散的巨噬细胞上，表现出相互排斥的模式。MMP9 的表达模式与 CD11c 重叠，这意味着 CD11c 巨噬细胞可能是 MMP9 的来源。我们的数据揭示了 GSS 微环境中巨噬细胞的特征，并为应用 MMP9 抑制剂预防 GSS 皮肤松弛提供了理论依据。
