Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
J Crohns Colitis. 2024 Feb 26;18(2):223-232. doi: 10.1093/ecco-jcc/jjad141.
Creeping fat [CF] is a poorly understood feature of Crohn's disease [CD], characterized by the wrapping of mesenteric adipose tissue [MAT] around the inflamed intestine. The aim of this study was to investigate the transcriptional profile and compositional features of CF.
We collected 59 MAT samples: 23 paired samples from patients with CD (CF [CD-CF] and MAT around the uninflamed intestine [CD-MAT]) and 13 MAT samples from non-CD patients [Con-MAT]. Differentially expressed gene [DEG], functional pathway, cell deconvolution, and gene co-expression network analyses were performed.
By comparing three different MAT samples, we identified a total of 529 DEGs [|log2FoldChange| > 1.5; false discovery rate < 0.05]. Of these, 323 genes showed an incremental pattern from Con-MAT to CD-MAT, and to CD-CF, while 105 genes displayed a decremental pattern. Genes with an incremental pattern were related to immune cell responses, including B- and T-cell activation, while genes with a decremental pattern were involved in cell trafficking and migration. Cell deconvolution analysis revealed significant changes in cellular composition between the CD-CF and Con-MAT groups, with increased proportions of B-cells/plasma cells [p = 1.16 × 10-4], T-cells [p = 3.66 × 10-3], and mononuclear phagocytes [p = 3.53 × 10-2] in the CD-CF group. In contrast, only the B-cell/plasma cell component showed a significant increase [p = 1.62 × 10-2] in the CD-MAT group compared to Con-MAT.
The distinct transcriptional profiles and altered cellular components of each MAT found in our study provide insight into the mechanisms behind CF and highlight its possible role in the pathogenesis of CD.
肠壁脂肪蔓延（CF）是克罗恩病（CD）中一种尚未被充分认识的特征，其表现为肠系膜脂肪组织（MAT）围绕发炎的肠道包裹。本研究旨在探讨 CF 的转录谱和组成特征。
我们收集了 59 份 MAT 样本：23 对来自 CD 患者的样本（CF [CD-CF] 和 MAT 围绕未发炎的肠道 [CD-MAT]）和 13 份来自非 CD 患者的 MAT 样本 [Con-MAT]。进行差异表达基因（DEG）、功能途径、细胞去卷积和基因共表达网络分析。
通过比较三种不同的 MAT 样本，我们总共鉴定出 529 个 DEG [|log2FoldChange| > 1.5; false discovery rate < 0.05]。其中，323 个基因表现出从 Con-MAT 到 CD-MAT，再到 CD-CF 的递增模式，而 105 个基因表现出递减模式。具有递增模式的基因与免疫细胞反应有关，包括 B 和 T 细胞激活，而具有递减模式的基因则与细胞迁移和迁移有关。细胞去卷积分析显示，CD-CF 组和 Con-MAT 组之间细胞组成发生显著变化，CD-CF 组中 B 细胞/浆细胞 [p=1.16×10-4]、T 细胞 [p=3.66×10-3]和单核吞噬细胞 [p=3.53×10-2]的比例显著增加，而 CD-MAT 组中仅 B 细胞/浆细胞成分显著增加 [p=1.62×10-2]与 Con-MAT 相比。
本研究中发现的每种 MAT 的独特转录谱和改变的细胞成分提供了对 CF 背后机制的深入了解，并强调了其在 CD 发病机制中的可能作用。
