Details

Autor(en) / Beteiligte

• Friedrich, Matthias
• Pohin, Mathilde
• Jackson, Matthew A.
• Korsunsky, Ilya
• Bullers, Samuel J.
• Rue-Albrecht, Kevin
• Christoforidou, Zoe
• Sathananthan, Dharshan
• Thomas, Tom
• Ravindran, Rahul
• Tandon, Ruchi
• Peres, Raphael Sanches
• Sharpe, Hannah
• Wei, Kevin
• Watts, Gerald F. M.
• Mann, Elizabeth H.
• Geremia, Alessandra
• Attar, Moustafa
• McCuaig, Sarah
• Thomas, Lloyd
• Collantes, Elena
• Uhlig, Holm H.
• Sansom, Stephen N.
• Easton, Alistair
• Raychaudhuri, Soumya
• Travis, Simon P.
• Powrie, Fiona M.

Titel

IL-1-driven stromal–neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies

Ist Teil von

• Nature medicine, 2021-11, Vol.27 (11), p.1970-1981

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Transcriptomic and histological profiling of gut biopsies from multiple independent cohorts of patients with inflammatory bowel disease identifies distinct histopathological, molecular and cellular features associated with treatment response, providing insights for patient stratification and precision therapy.