CRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease.
CRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease.
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DOI：
10.1038/s41467-021-27385-3
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发表时间：
2021-12-09
影响因子：
16.6
通讯作者：
Schnabl B
中科院分区：
文献类型：
--
作者：
Duan Y;Chu H;Brandl K;Jiang L;Zeng S;Meshgin N;Papachristoforou E;Argemi J;Mendes BG;Wang Y;Su H;Sun W;Llorente C;Hendrikx T;Liu X;Hosseini M;Kisseleva T;Brenner DA;Bataller R;Ramachandran P;Karin M;Fu W;Schnabl B
免疫球蛋白超家族补体受体（CRIg）在肝脏巨噬细胞上表达，可直接结合补体成分C3b或革兰氏阳性菌，从而介导吞噬作用。CRIg在多种免疫介导的疾病中发挥重要作用，但目前尚不清楚其病原体识别和吞噬功能是如何维持体内平衡并预防疾病的。我们之前发现产细胞溶素的粪肠球菌与酒精性肝病的严重程度相关。在此，我们证实酒精性肝病患者肝脏组织中的CRIg减少。与野生型小鼠相比，CRIg基因敲除小鼠发生更严重的乙醇诱导性肝病；Toll样受体2缺失则可减轻疾病严重程度。CRIg基因敲除小鼠清除从肠道移位至肝脏的革兰氏阳性菌（如粪肠球菌）的效率低于野生型小鼠。给予可溶性细胞外结构域CRIg-Ig蛋白可保护小鼠免受乙醇诱导的脂肪性肝炎。我们的研究结果表明，乙醇通过降低肝脏CRIg水平，损害肝脏对移位致病共生菌的清除，从而促进肝脏疾病进展。
CRIg在肝脏巨噬细胞上表达，可结合革兰氏阳性菌并介导吞噬作用，但尚不清楚其吞噬功能如何影响肝脏内环境稳定或疾病发生。本文作者报道，乙醇通过降低肝脏CRIg水平，损害肝脏对移位致病共生菌的清除，进而促进酒精性肝病的进展。
Complement receptor of immunoglobulin superfamily (CRIg) is expressed on liver macrophages and directly binds complement component C3b or Gram-positive bacteria to mediate phagocytosis. CRIg plays important roles in several immune-mediated diseases, but it is not clear how its pathogen recognition and phagocytic functions maintain homeostasis and prevent disease. We previously associated cytolysin-positive Enterococcus faecalis with severity of alcohol-related liver disease. Here, we demonstrate that CRIg is reduced in liver tissues from patients with alcohol-related liver disease. CRIg-deficient mice developed more severe ethanol-induced liver disease than wild-type mice; disease severity was reduced with loss of toll-like receptor 2. CRIg-deficient mice were less efficient than wild-type mice at clearing Gram-positive bacteria such as Enterococcus faecalis that had translocated from gut to liver. Administration of the soluble extracellular domain CRIg–Ig protein protected mice from ethanol-induced steatohepatitis. Our findings indicate that ethanol impairs hepatic clearance of translocated pathobionts, via decreased hepatic CRIg, which facilitates progression of liver disease. CRIg is expressed on liver macrophages and binds Gram-positive bacteria to mediate phagocytosis, but it is not clear how its phagocytic functions contribute to liver homeostasis or disease. Here the authors report that ethanol impairs hepatic clearance of translocated pathobionts, via decreased hepatic CRIg, which facilitates progression of alcoholic liver disease.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
16.6
作者：
MacParland SA;Liu JC;Ma XZ;Innes BT;Bartczak AM;Gage BK;Manuel J;Khuu N;Echeverri J;Linares I;Gupta R;Cheng ML;Liu LY;Camat D;Chung SW;Seliga RK;Shao Z;Lee E;Ogawa S;Ogawa M;Wilson MD;Fish JE;Selzner M;Ghanekar A;Grant D;Greig P;Sapisochin G;Selzner N;Winegarden N;Adeyi O;Keller G;Bader GD;McGilvray ID
通讯作者：
McGilvray ID
DOI：
10.1084/jem.20070432
发表时间：
2007-06-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Katschke KJ Jr;Helmy KY;Steffek M;Xi H;Yin J;Lee WP;Gribling P;Barck KH;Carano RA;Taylor RE;Rangell L;Diehl L;Hass PE;Wiesmann C;van Lookeren Campagne M
通讯作者：
van Lookeren Campagne M
影响因子：
9.8
作者：
Dominguez, Marlene;Rincon, Diego;Bataller, Ramon
通讯作者：
Bataller, Ramon
影响因子：
24.5
作者：
Forrest, EH;Evans, CDJ;Morris, AJ
通讯作者：
Morris, AJ