Primary sclerosing cholangitis displays distinct colonic mucosa topography yet a shared mast cell state with ulcerative colitis
- Author(s)
- Tearle, JL; Sviriaeva, E; Zhang, F; Jackson, KJ; Kaye, J; Tavakoli, P; Koentgen, S; Warren, J; Liang, RR; Malhotra, P; Williams, C; Haque, A; Arzivian, A; Sudhakar, KK; Neavin, D; Tedla, N; Kim, A; Haifer, C; King, HW; Hold, GL; Ghaly, S; James, KR;
- Journal Title
- Nature Communications
- Publication Type
- Jul 7
- Abstract
- Primary sclerosing cholangitis (PSC) is a chronic, progressing cholestatic disease that often co-occurs with inflammatory bowel disease (PSC-IBD). PSC-IBD affecting the colon (PSC-ulcerative colitis or PSC-UC) resembles clinical UC, but is characterised by less severe disease flares, right-colon predominance, and a greater lifetime risk of colorectal cancer than UC alone. To elucidate differences in the underlying biology between PSC-UC and UC, here we combine single-cell mRNA and antigen receptor sequencing, 16S ribosomal RNA gene analysis and spatial transcriptomics on biopsies from four colon regions of patients with PSC-UC and UC during endoscopic remission or at the time of relapse. We show that the PSC-UC colon, compared to healthy control (HC) or UC colon, harbours distinct and region-specific mucosal-adherent microbial communities and an enrichment of activated CD8 T and γδ T cells at the right colon, even in the absence of histological inflammation. By contrast, a TMEM176B(+) mast cell population that may be pro-tumourigenic is enriched in the colon during disease relapse in both PSC-UC and UC colon. These results highlight that the PSC-UC and UC colonic mucosa are fundamentally different while sharing similar cell programmes during active disease. Our data thus provide insights to guide tailored clinical management and precision therapies.
- Publisher
- Springer Nature
- Research Division(s)
- Genetics and Gene Regulation
- PubMed ID
- 42414303
- Publisher's Version
- https://doi.org/10.1038/s41467-026-75231-1
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-026-75231-1- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-07-09 08:59:11
Last Modified: 2026-07-09 08:59:18