PRIMARY sclerosing cholangitis (PSC) and ulcerative colitis (UC) exhibit distinct colonic mucosa topography but share similar cell programmes during active disease, providing insights that could help guide tailored clinical management, according to a new study.
PSC-UC
PSC is a chronic, progressing cholestatic disease that frequently co-occurs with inflammatory bowel disease (PSC-IBD).
When PSC affects the colon, it is referred to as PSC-ulcerative colitis (PSC-UC). Although PSC-UC resembles conventional UC, it is characterised by less severe disease flares, right-sided colonic predominance, and a greater lifetime risk of colorectal cancer than UC alone.
The aim of this study was to reveal the differences in the fundamental biology between PSC-UC and UC.
Distinct Mucosa Topography in PSC-UC
Researchers combined 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.
Results indicated that the PSC-UC colon harboured distinct mucosal-adherent microbial communities when compared to healthy controls and the UC colon. These mucosal-adherent communities were also region-specific.
Interestingly, the researchers also identified an enrichment of activated CD8 T cells and γδ T cells at the right colon, even in the absence of histological inflammation.
Mast Cell Population
Contrastingly, a potentially pro-tumourigenic TMEM176B+ mast cell population was enriched in the colon during disease relapse in both PSC-UC and UC.
The findings suggest that despite fundamental biological differences between the two conditions, they share similar cell programmes during active disease, including this mast cell state.
Conclusion
The study demonstrates that PSC-UC and UC are biologically distinct diseases with distinct colonic mucosal topographies, despite sharing common immune cell programmes during active disease. According to the authors, these findings provide insights that may help inform more tailored clinical management and the development of precision therapies for patients with PSC-UC.
Reference
Tearle JL et al. Primary sclerosing cholangitis displays distinct colonic mucosa topography yet a shared mast cell state with ulcerative colitis. Nat Commun. 2026;DOI:10.1038/s41467-026-75231-1.
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