A lncRNA from an inflammatory bowel disease risk locus maintains intestinal host-commensal homeostasis

Author:

Ma Hongdi,Hu Taidou,Tao Wanyin,Tong Jiyu,Han Zili,Herndler-Brandstetter Dietmar,Wei ZhengORCID,Liu Ruize,Zhou Tingyue,Liu Qiuyuan,Xu Xuemei,Zhang Kaiguang,Zhou RongbinORCID,Cho Judy H.,Li Hua-BingORCID,Huang Hailiang,Flavell Richard A.ORCID,Zhu ShuORCID

Abstract

AbstractInflammatory bowel diseases (IBD) are known to have complex, genetically influenced etiologies, involving dysfunctional interactions between the intestinal immune system and the microbiome. Here, we characterized how the RNA transcript from an IBD-associated long non-coding RNA locus (“CARINH-Colitis Associated IRF1 antisense Regulator of Intestinal Homeostasis”) protects against IBD. We show that CARINH and its neighboring gene coding for the transcription factor IRF1 together form a feedforward loop in host myeloid cells. The loop activation is sustained by microbial factors, and functions to maintain the intestinal host-commensal homeostasis via the induction of the anti-inflammatory factor IL-18BP and anti-microbial factors called guanylate-binding proteins (GBPs). Extending these mechanistic insights back to humans, we demonstrate that the function of the CARINH/IRF1 loop is conserved between mice and humans. Genetically, the T allele of rs2188962, the most probable causal variant of IBD within the CARINH locus from the human genetics study, impairs the inducible expression of the CARINH/IRF1 loop and thus increases genetic predisposition to IBD. Our study thus illustrates how an IBD-associated lncRNA maintains intestinal homeostasis and protects the host against colitis.

Funder

Broad Institute | Stanley Center for Psychiatric Research, Broad Institute

Publisher

Springer Science and Business Media LLC

Subject

Cell Biology,Molecular Biology

Cited by 17 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3