Abstract Background The mesentery, including creeping fat, has been increasingly recognized as an active contributor to Crohn’s disease (CD) progression. Previous studies demonstrated that mesenteric remodeling including mesenteric fibrosis may precede intestinal damage in the pathogenesis of CD. This study aimed to characterize the ultrastructural features of mesenteric adipose tissue to define the pro-fibrotic niche and reveal the pathogenesis of CD. Methods Mesenteric adipose tissues were collected from patients with CD undergoing intestinal resection (CD-Inflamed-Mes, CD-Uninflamed-Mes and CD-Uninvolved-Mes) and from patients undergoing colorectal resection for huge benign polyps (Normal-Mes) between September 2023 and July 2025. Tissues were fixed in glutaraldehyde and osmium tetroxide, embedded in epoxy resin, sectioned at 60 nm, stained with uranyl acetate and lead citrate, and examined using transmission electron microscopy (TEM, H-7650, 80 kV). Myofibroblast activation was assessed by α-SMA immunofluorescence. Results Normal mesenteric adipose tissue displayed thin stromal septa, uniform adipocytes, stable microvascular and lymphatic lumens, and minimal collagen deposition (Fig. 1A). In contrast, CD mesenteric adipose tissue displayed similar pathological alterations across CD-Inflamed-Mes, CD-Uninflamed-Mes, and CD-Uninvolved-Mes regions, indicating that these changes occur independently of local mucosal inflammation of the intestine. These alterations included thickened fibrotic septa with dense and irregular collagen bundles (Fig. 1B) distorted or partially collapsed microvessels with red blood cell extravasation (Fig. 1C) and increased mononuclear cell infiltration with apoptotic debris and frequent efferocytosis (Fig. 1D, 1E). Notably, stromal septa contained numerous fibroblast-like cells suggestive of activated mesenchymal remodeling (Fig. 1F). α-SMA staining confirmed the presence of activated myofibroblasts within septal stromal compartments, indicating ongoing fibroblast to myofibroblast transition (Fig. 2). The combined presence of stromal expansion, vascular instability, and immune activation indicated a persistent inflammatory-fibrotic microenvironment. Conclusion Mesenteric adipose tissue in CD contains a distinct pro-fibrotic inflammatory niche characterized by stromal remodeling and microvascular dysfunction, accompanied by persistent immune cell activity. These ultrastructural alterations are present even in mesenteric areas lacking overt intestinal inflammation, supporting the mesentery as an early pathogenic contributor and a potential therapeutic target in CD pathogenesis. Conflict of interest: Ms. Joo, Yang Hee: No conflict of interest Song, Eun Mi: No conflict of interest Park, Yehyun: No conflict of interest Choe, A Reum: No conflict of interest Byeon, Ju Ran: No conflict of interest Noh, Gyoung Tae: No conflict of interest Kim, Ho Seung: No conflict of interest Choi, Euno: No conflict of interest Byun, Jieun: No conflict of interest Park, Jihye: No conflict of interest Ahn, Yong-Ho: No conflict of interest Jung, Sung-Ae: Non-financial support
Jung et al. (Thu,) studied this question.