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Using CD FSL patient resection samples, we identify and quantify novel pathological changes in structure, collagen, and cell numbers for each ileal layer (mucosa, muscularis mucosae, submucosa, muscularis propria, serosa). In addition, fresh resection ileal samples were single\u2010cell RNA (scRNA)\u2010sequenced, validating the cell types and cell\u2013cell interactions. We found significantly increased collagenous fibrosis expansion, significantly increased infiltration of lymphocytes, macrophages, endothelium, and Crohn's lymphoid aggregates (CLAs) in all layers, except for the ulcerated mucosa. Importantly, endothelial cells accumulate in clusters around CLAs, and scRNA\u2010seq data demonstrated ligand\u2013receptor intercellular signalling interactions between endothelium, B and T lymphocytes, macrophages, and myofibroblasts via multiple pathways that included GAS, SELL, and SELPLG, among many others. The highest levels of fibrotic collagen and CLAs with accumulated endothelium were observed in submucosa, followed by serosa, demonstrating colocalisation and correlation of endothelial\u2010CLAs with collagen that is consistent with CLAs having a role in promoting collagenous fibrosis that requires further investigation. \u00a9 2026 The Author(s).\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70019","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T07:13:08Z","timestamp":1770361988000},"page":"398-412","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Crohn's lymphoid aggregates with endothelial clusters colocalise with submucosal fibrosis in fibrostenosing Crohn's 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