G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis.
G-protein coupled receptor 35 (GPR35) regulates the colonic epithelial cell response to enterotoxigenic Bacteroides fragilis.
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DOI：
10.1038/s42003-021-02014-3
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发表时间：
2021-05-14
影响因子：
5.9
通讯作者：
Sears CL
中科院分区：
文献类型：
--
作者：
Boleij A;Fathi P;Dalton W;Park B;Wu X;Huso D;Allen J;Besharati S;Anders RA;Housseau F;Mackenzie AE;Jenkins L;Milligan G;Wu S;Sears CL
G蛋白偶联受体（GPR）35在胃肠道中高度表达，主要在结肠上皮细胞（CEC）中表达，并与炎症性肠病（IBD）相关，提示其在胃肠道炎症中起作用。产肠毒素的脆弱拟杆菌（ETBF）毒素（BFT）是引起人类和动物肠道炎症的重要毒力因子。我们通过GPR35确定了BFT信号。使用GPR35拮抗剂ML145阻断GPR35在CECs中的功能，结合shRNA敲除和crisprcas介导的敲除，通过E-cadherin切割、β -阻滞素募集和IL-8分泌测量，导致CECs对BFT的反应降低。重要的是，在小鼠模型中，GPR35是etbf诱导的结肠炎快速发作所必需的。与野生型C57Bl6小鼠相比，gpr35缺陷小鼠的死亡率和疾病严重程度降低。我们的数据支持GPR35在CEC和粘膜对BFT的反应中的作用，并强调了该分子在结肠中感知ETBF的重要性。Boleij等人发现G蛋白偶联受体35 （GPR35）调节结肠上皮细胞对产肠毒素的脆弱拟杆菌（ETBF）的反应。他们发现GPR35缺乏几乎可以保护小鼠免受ETBF诱导的死亡，这表明GPR35在结肠中感知ETBF的重要性。
G protein-coupled receptor (GPR)35 is highly expressed in the gastro-intestinal tract, predominantly in colon epithelial cells (CEC), and has been associated with inflammatory bowel diseases (IBD), suggesting a role in gastrointestinal inflammation. The enterotoxigenic Bacteroides fragilis (ETBF) toxin (BFT) is an important virulence factor causing gut inflammation in humans and animal models. We identified that BFT signals through GPR35. Blocking GPR35 function in CECs using the GPR35 antagonist ML145, in conjunction with shRNA knock-down and CRISPRcas-mediated knock-out, resulted in reduced CEC-response to BFT as measured by E-cadherin cleavage, beta-arrestin recruitment and IL-8 secretion. Importantly, GPR35 is required for the rapid onset of ETBF-induced colitis in mouse models. GPR35-deficient mice showed reduced death and disease severity compared to wild-type C57Bl6 mice. Our data support a role for GPR35 in the CEC and mucosal response to BFT and underscore the importance of this molecule for sensing ETBF in the colon. Boleij et al. show that G protein-coupled receptor 35 (GPR35) regulates the responses to enterotoxigenic Bacteroides fragilis (ETBF) in colonic epithelial cells. They find that GPR35-deficiency nearly protected mice from ETBF-induced death, suggesting the importance of GPR35 in sensing ETBF in the colon.
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影响因子：
5.7
作者：
Okumura, S;Baba, H;Ikenaka, K
通讯作者：
Ikenaka, K
影响因子：
30.8
作者：
Imielinski, Marcin;Baldassano, Robert N.;Griffiths, Anne;Russell, Richard K.;Annese, Vito;Dubinsky, Marla;Kugathasan, Subra;Bradfield, Jonathan P.;Walters, Thomas D.;Sleiman, Patrick;Kim, Cecilia E.;Muise, Aleixo;Wang, Kai;Glessner, Joseph T.;Saeed, Shehzad;Zhang, Haitao;Frackelton, Edward C.;Hou, Cuiping;Flory, James H.;Otieno, George;Chiavacci, Rosetta M.;Grundmeier, Robert;Castro, Massimo;Latiano, Anna;Dallapiccola, Bruno;Stempak, Joanne;Abrams, Debra J.;Taylor, Kent;McGovern, Dermot;Heyman, Melvin B.;Ferry, George D.;Kirschner, Barbara;Lee, Jessica;Essers, Jonah;Grand, Richard;Stephens, Michael;Levine, Arie;Piccoli, David;Van Limbergen, Johan;Cucchiara, Salvatore;Monos, Dimitri S.;Guthery, Stephen L.;Denson, Lee;Wilson, David C.;Grant, Struan F. A.;Daly, Mark;Silverberg, Mark S.;Satsangi, Jack;Hakonarson, Hakon
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Hakonarson, Hakon
影响因子：
30.3
作者：
Chung L;Thiele Orberg E;Geis AL;Chan JL;Fu K;DeStefano Shields CE;Dejea CM;Fathi P;Chen J;Finard BB;Tam AJ;McAllister F;Fan H;Wu X;Ganguly S;Lebid A;Metz P;Van Meerbeke SW;Huso DL;Wick EC;Pardoll DM;Wan F;Wu S;Sears CL;Housseau F
通讯作者：
Housseau F
影响因子：
7.3
作者：
Deng, Huayun;Hu, Haibei;He, Mingqian;Hu, Jieyu;Niu, Weijun;Ferrie, Ann M.;Fang, Ye
通讯作者：
Fang, Ye
影响因子：
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作者：
Franco, AA;Buckwold, SL;Sears, CL
通讯作者：
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