Spatiotemporal analysis reveals distinct inflammatory programs underlying chronic colitis
spontaneous colitis models, including anti-IL-12p40 intervention, and integrated time-course transcriptomic analyses at bulk, single-cell, and spatial resolution. These well-established models exhibited conserved features of chronic inflammation, including neutrophil infiltration, and impaired tissue regeneration. Comparison of murine transcriptional programs and human IBD datasets revealed neutrophil-associated inflammation and cytokine signaling as the most conserved pathways across species. We identified spatial heterogeneity in inflammatory modules and described three gene programs with differential spatial and temporal distributions, including one corresponding to tertiary lymphoid structures. When used together, these models recapitulate complementary aspects of human disease at both cellular and transcriptional levels. This high-resolution spatiotemporal atlas will guide future translational research aimed at optimizing therapeutic strategies for IBD.
Authors
- Hailey Sounart (ORCID: https://orcid.org/0009-0000-5772-3961)
- Stefania Giacomello (ORCID: https://orcid.org/0000-0003-0738-1574)
- Jennifer Fransson (ORCID: https://orcid.org/0000-0003-4762-901X)
- Chiara Zagami (ORCID: https://orcid.org/0000-0002-5246-3432)
- Chiara Sorini (ORCID: https://orcid.org/0000-0002-6803-8377)
- Yuhao Chi (ORCID: https://orcid.org/0009-0003-2526-6489)
- Srustidhar Das (ORCID: https://orcid.org/0000-0002-0833-588X)
- Rebeca F. Cardoso (ORCID: https://orcid.org/0000-0003-4423-0847)
- Philip Smith (ORCID: https://orcid.org/0000-0002-2295-7204)
- Eduardo J. Villablanca (ORCID: https://orcid.org/0000-0001-9522-9729)
- Martin Suarez-Alvarez (ORCID: https://orcid.org/0009-0003-6420-1362)
- María Teresa Ulloa (ORCID: https://orcid.org/0009-0005-0009-9340)
- Ali Okhovat
- Anna Mechling
- Charlotte R. H. Hedin
- Rodrigo A. Morales Castro
- Francisca Castillo
- Ning He
Institutions
- Roche (Switzerland) (CH)
- Karolinska University Hospital (SE)
- Science for Life Laboratory (SE)
- KTH Royal Institute of Technology (SE)
Publication Details
- Journal
- Immunity
- Published
- 2026-05-01
- DOI
- https://doi.org/10.1016/j.immuni.2026.04.005
- Primary Topic
- Inflammatory Bowel Disease
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Cancerfonden
- Knut och Alice Wallenbergs Stiftelse
- Vetenskapsrådet
- Ruth och Richard Julins Stiftelse
- H2020 European Research Council