IL-1-driven stromal-neutrophil interactions define a subset of patients with inflammatory bowel disease that does not respond to therapies.
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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DOI：
10.1038/s41591-021-01520-5
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发表时间：
2021-11
期刊：
影响因子：
82.9
通讯作者：
Powrie FM
中科院分区：
文献类型：
--
作者：
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;Oxford IBD Cohort Investigators;Roche Fibroblast Network Consortium;McCuaig S;Thomas L;Collantes E;Uhlig HH;Sansom SN;Easton A;Raychaudhuri S;Travis SP;Powrie FM
目前的炎症性肠病（IBD）治疗在高比例的患者中无效。通过对三组IBD患者（共376例）进行整体和单细胞转录组学、定量组织病理学和原位定位，我们确定了IBD异质性组织炎症反应中的共表达基因模块，这些基因模块映射到不同的组织病理学和细胞特征（病理类型）。这些病理类型之一是由高中性粒细胞浸润，成纤维细胞的活化和血管重塑在深溃疡部位定义的。溃疡床中活化的成纤维细胞显示IL-1 R而非TNF依赖的嗜中性粒细胞化学引诱物特性。在4个独立队列中，对几种治疗无应答者的病理型相关中性粒细胞和成纤维细胞特征增加（总n = 343）。不同的，局部的，组织病理类型的鉴定将有助于精确靶向目前的治疗方法，并提供了一个生物学原理的IL-1信号传导阻滞在溃疡性疾病。来自多个独立炎症性肠病患者队列的肠道活检的转录组学和组织学分析鉴定了与治疗反应相关的不同组织病理学、分子和细胞特征，为患者分层和精确治疗提供了见解。
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.
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
64.5
作者：
Kinchen J;Chen HH;Parikh K;Antanaviciute A;Jagielowicz M;Fawkner-Corbett D;Ashley N;Cubitt L;Mellado-Gomez E;Attar M;Sharma E;Wills Q;Bowden R;Richter FC;Ahern D;Puri KD;Henault J;Gervais F;Koohy H;Simmons A
通讯作者：
Simmons A
影响因子：
16.6
作者：
Haberman, Yael;Karns, Rebekah;Denson, Lee A.
通讯作者：
Denson, Lee A.
DOI：
10.1084/jem.20111453
发表时间：
2012-08-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coccia M;Harrison OJ;Schiering C;Asquith MJ;Becher B;Powrie F;Maloy KJ
通讯作者：
Maloy KJ