IL-1-driven stromal–neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies
Current inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology and in situ localization across three cohorts of patients with IBD (total n = 376), we identify coexpressed gene modules wi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2021
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| _version_ | 1826296144960946176 |
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| author | Friedrich, M Pohin, M Jackson, MA Korsunsky, I Bullers, SJ Rue-Albrecht, K Christoforidou, Z Sathananthan, D Thomas, T Ravindran, R Tandon, R Peres, RS Sharpe, H Wei, K Watts, GFM Mann, EH Geremia, A Attar, M Barone, F Brenner, M Buckley, CD Coles, M Frei, AP Lassen, KG Powrie, FM McCuaig, S Thomas, L Collantes, E Uhlig, HH Sansom, SN Easton, A Raychaudhuri, S Travis, SP Powrie, FM |
| author_facet | Friedrich, M Pohin, M Jackson, MA Korsunsky, I Bullers, SJ Rue-Albrecht, K Christoforidou, Z Sathananthan, D Thomas, T Ravindran, R Tandon, R Peres, RS Sharpe, H Wei, K Watts, GFM Mann, EH Geremia, A Attar, M Barone, F Brenner, M Buckley, CD Coles, M Frei, AP Lassen, KG Powrie, FM McCuaig, S Thomas, L Collantes, E Uhlig, HH Sansom, SN Easton, A Raychaudhuri, S Travis, SP Powrie, FM |
| author_sort | Friedrich, M |
| collection | OXFORD |
| description | Current inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology and in situ localization across three cohorts of patients with IBD (total n = 376), we identify coexpressed gene modules within the heterogeneous tissular inflammatory response in IBD that map to distinct histopathological and cellular features (pathotypes). One of these pathotypes is defined by high neutrophil infiltration, activation of fibroblasts and vascular remodeling at sites of deep ulceration. Activated fibroblasts in the ulcer bed display neutrophil-chemoattractant properties that are IL-1R, but not TNF, dependent. Pathotype-associated neutrophil and fibroblast signatures are increased in nonresponders to several therapies across four independent cohorts (total n = 343). The identification of distinct, localized, tissular pathotypes will aid precision targeting of current therapeutics and provides a biological rationale for IL-1 signaling blockade in ulcerating disease. |
| first_indexed | 2024-03-07T04:11:49Z |
| format | Journal article |
| id | oxford-uuid:c8129cb9-dd1c-4b05-a15c-68d6a3df224c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:11:49Z |
| publishDate | 2021 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:c8129cb9-dd1c-4b05-a15c-68d6a3df224c2022-03-27T06:49:52ZIL-1-driven stromal–neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapiesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c8129cb9-dd1c-4b05-a15c-68d6a3df224cEnglishSymplectic ElementsSpringer Nature2021Friedrich, MPohin, MJackson, MAKorsunsky, IBullers, SJRue-Albrecht, KChristoforidou, ZSathananthan, DThomas, TRavindran, RTandon, RPeres, RSSharpe, HWei, KWatts, GFMMann, EHGeremia, AAttar, MBarone, FBrenner, MBuckley, CDColes, MFrei, APLassen, KGPowrie, FMMcCuaig, SThomas, LCollantes, EUhlig, HHSansom, SNEaston, ARaychaudhuri, STravis, SPPowrie, FMCurrent inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology and in situ localization across three cohorts of patients with IBD (total n = 376), we identify coexpressed gene modules within the heterogeneous tissular inflammatory response in IBD that map to distinct histopathological and cellular features (pathotypes). One of these pathotypes is defined by high neutrophil infiltration, activation of fibroblasts and vascular remodeling at sites of deep ulceration. Activated fibroblasts in the ulcer bed display neutrophil-chemoattractant properties that are IL-1R, but not TNF, dependent. Pathotype-associated neutrophil and fibroblast signatures are increased in nonresponders to several therapies across four independent cohorts (total n = 343). The identification of distinct, localized, tissular pathotypes will aid precision targeting of current therapeutics and provides a biological rationale for IL-1 signaling blockade in ulcerating disease. |
| spellingShingle | Friedrich, M Pohin, M Jackson, MA Korsunsky, I Bullers, SJ Rue-Albrecht, K Christoforidou, Z Sathananthan, D Thomas, T Ravindran, R Tandon, R Peres, RS Sharpe, H Wei, K Watts, GFM Mann, EH Geremia, A Attar, M Barone, F Brenner, M Buckley, CD Coles, M Frei, AP Lassen, KG Powrie, FM McCuaig, S Thomas, L Collantes, E Uhlig, HH Sansom, SN Easton, A Raychaudhuri, S Travis, SP Powrie, FM IL-1-driven stromal–neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies |
| title | IL-1-driven stromal–neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies |
| title_full | IL-1-driven stromal–neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies |
| title_fullStr | IL-1-driven stromal–neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies |
| title_full_unstemmed | IL-1-driven stromal–neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies |
| title_short | IL-1-driven stromal–neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies |
| title_sort | il 1 driven stromal neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies |
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