| 2 | A lncRNA from an inflammatory bowel disease risk locus maintains intestinal host-commensal homeostasis显示文摘Inflammatory 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. | Hongdi Ma Taidou Hu Wanyin Tao Jiyu Tong Zili Han Dietmar Herndler-Brandstetter Zheng Wei Ruize Liu Tingyue Zhou Qiuyuan Liu Xuemei Xu Kaiguang Zhang Rongbin Zhou Judy H.Cho Hua-Bing Li Hailiang Huang Richard A.Flavell Shu Zhu | 2023 | Cell Research2023，33，5： | 0 |
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