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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
Nature medicine, 11/2021, Letnik: 27, Številka: 11Journal Article
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.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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