Abstract
Small bowel strictures remain a debilitating consequence of Crohn’s disease and contribute to poor outcomes for patients. Recently, TGFβ has been identified as an important driver of intestinal fibrosis. We studied the localization of TGFβ isoforms in ileal strictures of patients with Crohn’s disease using in situ hybridization to understand TGFβ’s role in stricture formation. The mucosa of strictures was characterized by higher TGFβ1 while the stricture submucosa showed higher TGFβ3 compared to normal ileum from patients without Crohn’s disease (p = 0.02 and p = 0.044, respectively). We correlated these findings with single-cell transcriptomics which demonstrated that TGFβ3 transcripts overall are very rare, which may partially explain why its role in intestinal fibrosis has remained unclear to date. There were no significant differences in fibroblast or B cell TGFβ1 and/or TGFβ3 expression in inflamed vs. noninflamed ileum. We discuss the implications of these findings for therapeutic development strategies to treat patients with fibrostenotic Crohn’s disease.
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Acknowledgements
We gratefully acknowledge the contribution of samples by William Faubion (Mayo Clinic, Rochester, MN). We gratefully acknowledge project conceptual input from Steve Hurst (Genentech Inc, South San Francisco, CA).
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Financial support for this project was provided by Genentech Inc, South San Francisco, CA, USA.
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Project conceptualization: SL, JZ, RS, SBG, TS, KP, JM, MK. Data curation: SL, IK, VI, JZ, JG. Methodologies: SL, IK, VI, JZ, JG. Formal analysis: SL, IK, VI, JZ, JG. Original draft of manuscript: SL. Editing and final approval of manuscript: all authors.
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Levitte, S., Khan, I., Iyahen, V. et al. Differential expression of small bowel TGFβ1 and TGFβ3 characterizes intestinal strictures in patients with fibrostenotic Crohn’s disease. Histochem Cell Biol (2024). https://doi.org/10.1007/s00418-024-02290-0
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DOI: https://doi.org/10.1007/s00418-024-02290-0