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Multiplex spatial omics reveals changes in immune-epithelial crosstalk during inflammation and dysplasia development in chronic IBD patients

Authors :
Matthijs J.D. Baars
Evelien Floor
Neeraj Sinha
José J.M. ter Linde
Stephanie van Dam
Mojtaba Amini
Isaäc J. Nijman
Joren R. ten Hove
Julia Drylewicz
G.Johan A. Offerhaus
Miangela M. Laclé
Bas Oldenburg
Yvonne Vercoulen
Source :
iScience, Vol 27, Iss 8, Pp 110550- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Summary: Patients with long-standing inflammatory bowel disease (IBD) face an increased risk of developing colitis-associated cancer (CAC). Although IBD-induced prolonged inflammation seems to be involved in CAC pathogenesis, the specific molecular changes that contribute remain unknown. Here, we applied digital spatial RNA profiling, RNAscope, and imaging mass cytometry to examine paired uninflamed, inflamed, and early dysplastic mucosa of patients with IBD. We observed robust type 3 (IL-17) responses during inflammation, accompanied by elevated JAK-STAT signaling and phosphorylated STAT3 (P-STAT3) levels, with both inflamed and dysplastic mucosa displaying immune cell activation. Higher stromal P-STAT3 was detected in uninflamed and inflamed mucosa of patients who eventually developed dysplasia. CD8a+ T cells did not infiltrate inflamed or dysplastic epithelial regions in these patients, while control patients showed elevated CD8a in inflamed mucosa. Our study reveals distinct inflammatory patterns throughout CAC development, marked by an activated IL-17 pathway, engaged STAT3, and diminished cytotoxic T cell infiltration.

Details

Language :
English
ISSN :
25890042
Volume :
27
Issue :
8
Database :
Directory of Open Access Journals
Journal :
iScience
Publication Type :
Academic Journal
Accession number :
edsdoj.589bcf3cd14349a187c71e387a5367fd
Document Type :
article
Full Text :
https://doi.org/10.1016/j.isci.2024.110550