Intelectin-1 binds and alters the localization of the mucus barrier-modifying bacterium Akkermansia muciniphila.
Intelectin-1 binds and alters the localization of the mucus barrier-modifying bacterium Akkermansia muciniphila.
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Intelectin-1 结合并改变粘液屏障修饰细菌 Akkermansia muciniphila 的定位。
DOI：
10.1084/jem.20211938
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发表时间：
2023-01-02
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影响因子：
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ITLN1的表达受未折叠蛋白反应的调节，它覆盖了包括嗜粘阿克曼氏菌在内的一组微生物，使它们能够变薄内黏液层，并增加结肠炎的严重程度。UC中ITLN1的上调可能会导致类似的结果。ITLN1是一种由肠上皮细胞（IECs）分泌的凝集素，在人溃疡性结肠炎（UC）中上调。我们利用小鼠模型研究了ITLN1在IECs中的产生是如何调控的，以及ITLN1在宿主-微生物群界面上的生物学效应。我们的数据显示，UC患者IECs中ITLN1的上调是激活未折叠蛋白反应的结果。对ITLN1包被的微生物在体内的分析揭示了一个有限的微生物亚群，包括嗜粘菌Akkermansia muciniphila。过表达肠道ITLN1的小鼠表现出结肠内黏液层厚度减少，嗜粘杆菌更接近上皮细胞表面，与UC中报道的变化相似。内黏液层的变化依赖于微生物群和嗜粘杆菌，并与对化学诱导和T细胞介导的结肠炎的敏感性增强有关。我们得出结论，通过确定一组选定的细菌在黏液层的定位，ITLN1改变了这一关键屏障。总之，这些发现可以解释ITLN1失调对UC发病机制的影响。
ITLN1, whose expression is regulated by the unfolded protein response, coats a subset of microorganisms, including Akkermansia muciniphila, allows them to thin the inner mucus layer, and increases colitis severity. ITLN1 upregulation in UC may drive similar outcomes. Intelectin-1 (ITLN1) is a lectin secreted by intestinal epithelial cells (IECs) and upregulated in human ulcerative colitis (UC). We investigated how ITLN1 production is regulated in IECs and the biological effects of ITLN1 at the host–microbiota interface using mouse models. Our data show that ITLN1 upregulation in IECs from UC patients is a consequence of activating the unfolded protein response. Analysis of microbes coated by ITLN1 in vivo revealed a restricted subset of microorganisms, including the mucolytic bacterium Akkermansia muciniphila. Mice overexpressing intestinal ITLN1 exhibited decreased inner colonic mucus layer thickness and closer apposition of A. muciniphila to the epithelial cell surface, similar to alterations reported in UC. The changes in the inner mucus layer were microbiota and A. muciniphila dependent and associated with enhanced sensitivity to chemically induced and T cell–mediated colitis. We conclude that by determining the localization of a select group of bacteria to the mucus layer, ITLN1 modifies this critical barrier. Together, these findings may explain the impact of ITLN1 dysregulation on UC pathogenesis.
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DOI：
10.1126/science.aay7367
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Bergstrom K;Shan X;Casero D;Batushansky A;Lagishetty V;Jacobs JP;Hoover C;Kondo Y;Shao B;Gao L;Zandberg W;Noyovitz B;McDaniel JM;Gibson DL;Pakpour S;Kazemian N;McGee S;Houchen CW;Rao CV;Griffin TM;Sonnenburg JL;McEver RP;Braun J;Xia L
通讯作者：
Xia L
影响因子：
4.6
作者：
Almalki F;Nonnecke EB;Castillo PA;Bevin-Holder A;Ullrich KK;Lönnerdal B;Odenthal-Hesse L;Bevins CL;Hollox EJ
通讯作者：
Hollox EJ
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
30.8
作者：
Ellinghaus D;Jostins L;Spain SL;Cortes A;Bethune J;Han B;Park YR;Raychaudhuri S;Pouget JG;Hübenthal M;Folseraas T;Wang Y;Esko T;Metspalu A;Westra HJ;Franke L;Pers TH;Weersma RK;Collij V;D'Amato M;Halfvarson J;Jensen AB;Lieb W;Degenhardt F;Forstner AJ;Hofmann A;International IBD Genetics Consortium (IIBDGC);International Genetics of Ankylosing Spondylitis Consortium (IGAS);International PSC Study Group (IPSCSG);Genetic Analysis of Psoriasis Consortium (GAPC);Psoriasis Association Genetics Extension (PAGE);Schreiber S;Mrowietz U;Juran BD;Lazaridis KN;Brunak S;Dale AM;Trembath RC;Weidinger S;Weichenthal M;Ellinghaus E;Elder JT;Barker JN;Andreassen OA;McGovern DP;Karlsen TH;Barrett JC;Parkes M;Brown MA;Franke A
通讯作者：
Franke A
影响因子：
64.8
作者：
通讯作者：
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