전사체 분석 기반 크론병 특이 장간막 지방 조직 비후의 역할 분석

Abstract

One of the pathologic features of Crohn’s disease (CD) is a “creeping fat” (CF), mesenteric adipose tissue (MAT) wrapping the inflamed intestine. This study aims to define distinct transcriptional profile and identify cellular composition of CD-CF. We collected 59 MAT samples: 23 paired samples from CD patients with 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) analysis performed by DESeq2, cell deconvolution analysis performed by CIBERSORTx. 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 showed a decremental pattern. Incremental pattern genes were related to immune cell responses, including B-cell 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-value=6.00E-08) and decreased proportions of preadipocytes (P-value=6.20E-04) in the CD-CF group. To conclude, dynamic transcriptional changes and altered cellular components may be crucial for the shift from Con-MAT to CD-MAT and to CD-CF, providing insight into the mechanisms behind CF and highlighting its possible role in CD pathogenesis.