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科学家揭示部分炎症性肠病患者对治疗无反应的原因
作者:小柯机器人 发布时间:2021/10/23 22:35:53

英国牛津大学Fiona M. Powrie课题组发现IL-1诱导的间质-中性粒细胞相互作用是部分炎症性肠病(IBD)患者对治疗无反应的原因。相关论文于2021年10月21日发表于国际学术期刊《自然-医学》杂志。

综合三组IBD患者的批量和单细胞转录组学、定量组织病理学和原位定位(总 n = 376),研究人员确定了IBD异质组织炎症反应中的共表达基因模块,这些模块映射到不同的组织病理学和细胞特征(病理)。这些病理特征之一是高中性粒细胞浸润、成纤维细胞活化和深部溃疡部位血管重塑。溃疡位点的活化成纤维细胞具有IL-1R而非TNF依赖性嗜中性粒细胞趋化特性。

在四个独立队列(总n = 343)中,对几种疗法无反应患者都具有相关病理性中性粒细胞和成纤维细胞增加。识别独特的、局部的、组织病理型将有助于当前治疗的精确靶向,并为溃疡性疾病中IL-1信号传导阻断提供生物学依据。

研究人员表示,现存炎症性肠病疗法对很多患者无效。

附:英文原文

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

Author: 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.

Issue&Volume: 2021-10-21

Abstract: 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.

DOI: 10.1038/s41591-021-01520-5

Source: https://www.nature.com/articles/s41591-021-01520-5

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex