GPR120 promotes neutrophil control of intestinal bacterial infection.
GPR120 promotes neutrophil control of intestinal bacterial infection.
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DOI：
10.1080/19490976.2023.2190311
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发表时间：
2023-01
期刊：
影响因子：
12.2
通讯作者：
中科院分区：
文献类型：
--
作者：
G蛋白偶联受体120（GPR 120）与抗炎功能有关。然而，GPR120如何调节中性粒细胞功能仍不清楚。本研究探讨了GPR120在调节中性粒细胞抗肠道细菌功能中的作用。16S rRNA测序用于测量野生型（WT）小鼠和Gpr120 −/−小鼠的肠道微生物群。在WT和Gpr120 −/−小鼠中进行啮齿类柠檬酸杆菌感染和葡聚糖硫酸钠（DSS）诱导的结肠炎模型。小鼠腹膜来源的原代中性粒细胞用于确定中性粒细胞功能。GPR120 −/−小鼠的微生物群组成发生了改变。Gpr120 −/−小鼠在感染或DSS损伤后清除肠道啮齿类柠檬酸杆菌的能力较低，肠道炎症更严重。中性粒细胞的消耗降低了啮齿类柠檬酸杆菌的肠道清除率。GPR120激动剂CpdA增强WT中性粒细胞产生活性氧（ROS）和细胞外陷阱（NET），而GPR120缺陷型中性粒细胞表现出较低水平的ROS和NET。CpdA处理的中性粒细胞表现出增强的抑制啮齿柠檬酸杆菌生长的能力，这被NET或ROS的抑制所废除。CpdA促进嗜中性粒细胞抑制大肠杆菌O9：H4和从克罗恩病患者分离的致病性大肠杆菌O83：H1的生长。mTOR激活和糖酵解介导的GPR120在中性粒细胞中对ROS和NET的机械诱导。此外，CpdA促进中性粒细胞产生IL-17和IL-22，并且用GPR120活化的中性粒细胞的条件培养基处理增加肠上皮细胞屏障功能。我们的研究证明了中性粒细胞中GPR120在保护肠道细菌入侵中的关键作用。
G-protein coupled receptor 120 (GPR 120) has been implicated in anti-inflammatory functions. However, how GPR120 regulates the neutrophil function remains unknown. This study investigated the role of GPR120 in the regulation of neutrophil function against enteric bacteria. 16S rRNA sequencing was used for measuring the gut microbiota of wild-type (WT) mice and Gpr120−/− mice. Citrobacter rodentium infection and dextran sulfate sodium (DSS)-induced colitis models were performed in WT and Gpr120−/− mice. Mouse peritoneal-derived primary neutrophils were used to determine the neutrophil functions. Gpr120−/− mice showed altered microbiota composition. Gpr120−/− mice exhibited less capacity to clear intestinal Citrobacter rodentium and more severe intestinal inflammation upon infection or DSS insults. Depletion of neutrophils decreased the intestinal clearance of Citrobacter rodentium. GPR120 agonist, CpdA, enhanced WT neutrophil production of reactive oxygen species (ROS) and extracellular traps (NETs), and GPR120-deficient neutrophils demonstrated a lower level of ROS and NETs. CpdA-treated neutrophils showed an enhanced capacity to inhibit the growth of Citrobacter rodentium, which was abrogated by the inhibition of either NETs or ROS. CpdA promoted neutrophil inhibition of the growth of commensal bacteria Escherichia coli O9:H4 and pathobiont Escherichia coli O83:H1 isolated from a Crohn’s disease patient. Mechanically, mTOR activation and glycolysis mediated GPR120 induction of ROS and NETs in neutrophils. Additionally, CpdA promoted the neutrophil production of IL-17 and IL-22, and treatment with a conditioned medium of GPR120-activated neutrophils increased intestinal epithelial cell barrier functions. Our study demonstrated the critical role of GPR120 in neutrophils in protection against enteric bacterial invasion.
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DOI：
10.4049/jimmunol.1501541
发表时间：
2016-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chen F;Cao A;Yao S;Evans-Marin HL;Liu H;Wu W;Carlsen ED;Dann SM;Soong L;Sun J;Zhao Q;Cong Y
通讯作者：
Cong Y
影响因子：
4.4
作者：
Lazzaretto, Beatrice;Fadeel, Bengt
通讯作者：
Fadeel, Bengt
二十碳五烯酸通过 GPR120 诱导小鼠骨髓间充质干细胞适应性自噬，从而减弱地塞米松诱导的细胞凋亡
影响因子：
9
作者：
Gao B;Han YH;Wang L;Lin YJ;Sun Z;Lu WG;Hu YQ;Li JQ;Lin XS;Liu BH;Jie Q;Yang L;Luo ZJ
通讯作者：
Luo ZJ
DOI：
10.4049/jimmunol.1800003
发表时间：
2018-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chen F;Yang W;Huang X;Cao AT;Bilotta AJ;Xiao Y;Sun M;Chen L;Ma C;Liu X;Liu CG;Yao S;Dann SM;Liu Z;Cong Y
通讯作者：
Cong Y
影响因子：
4.4
作者：
Nash JH;Villegas A;Kropinski AM;Aguilar-Valenzuela R;Konczy P;Mascarenhas M;Ziebell K;Torres AG;Karmali MA;Coombes BK
通讯作者：
Coombes BK