LILRB2/PirB mediates macrophage recruitment in fibrogenesis of nonalcoholic steatohepatitis.
LILRB2/PirB mediates macrophage recruitment in fibrogenesis of nonalcoholic steatohepatitis.
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DOI：
10.1038/s41467-023-40183-3
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发表时间：
2023-07-22
影响因子：
16.6
通讯作者：
Yu, Xue-Feng
中科院分区：
文献类型：
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作者：
Li, Dan-Pei;Huang, Li;Kan, Ran-Ran;Meng, Xiao-Yu;Wang, Shu-Yun;Zou, Hua-Jie;Guo, Ya-Ming;Luo, Pei-Qiong;Pan, Li-Meng;Xiang, Yu-Xi;Mao, Bei-Bei;Xie, Yu-Yu;Wang, Zhi-Han;Yang, Min;He, Rui;Yang, Yan;Liu, Zhe-Long;Xie, Jun-Hui;Ma, De-Lin;Zhang, Ben-Ping;Shao, Shi-Ying;Chen, Xi;Xu, Si-Miao;He, Wen-Tao;Li, Wen-Jun;Chen, Yong;Yu, Xue-Feng
抑制免疫细胞的浸润和活化已被认为可以有效地改善非酒精性脂肪性肝炎（NASH）。配对免疫球蛋白样受体B（Pir B）及其人直系同源受体白细胞免疫球蛋白样受体B（LILRB 2）是免疫抑制性受体。然而，它们在NASH发病机制中的作用仍不清楚。在这里，我们证明了PirB/LILRB 2通过与其配体血管生成素样蛋白8（ANGPTL 8）结合来调节NASH期间巨噬细胞的迁移。肝细胞特异性ANGPTL 8敲除减少MDM浸润并解决NASH小鼠肝脏中的脂质积聚和纤维化进展。此外，PirB−/−骨髓（BM）嵌合体消除ANGPTL 8诱导的MDM向肝脏的迁移。然而，PirB胞外域蛋白可以通过隔离ANGPTL 8来改善NASH。此外，在人外周血单核细胞中也观察到LILRB 2-ANGPTL 8结合促进的MDM迁移和炎症活化。综上所述，我们的发现揭示了PirB/LILRB 2在NASH发病机制中的作用，并将PirB/LILRB 2-ANGPTL 8信号传导确定为NASH管理或治疗的潜在靶标。抑制免疫细胞浸润和活化已被认为可以改善非酒精性脂肪性肝炎的肝脏炎症和纤维化。在这里，作者表明PirB/LILRB 2通过与ANGPTL 8结合来调节NASH期间巨噬细胞的迁移，ANGPTL 8参与NASH发展的调节。
Inhibition of immunocyte infiltration and activation has been suggested to effectively ameliorate nonalcoholic steatohepatitis (NASH). Paired immunoglobulin-like receptor B (PirB) and its human ortholog receptor, leukocyte immunoglobulin-like receptor B (LILRB2), are immune-inhibitory receptors. However, their role in NASH pathogenesis is still unclear. Here, we demonstrate that PirB/LILRB2 regulates the migration of macrophages during NASH by binding with its ligand angiopoietin-like protein 8 (ANGPTL8). Hepatocyte-specific ANGPTL8 knockout reduces MDM infiltration and resolves lipid accumulation and fibrosis progression in the livers of NASH mice. In addition, PirB−/− bone marrow (BM) chimeras abrogate ANGPTL8-induced MDM migration to the liver. And yet, PirB ectodomain protein could ameliorate NASH by sequestering ANGPTL8. Furthermore, LILRB2-ANGPTL8 binding-promoted MDM migration and inflammatory activation are also observed in human peripheral blood monocytes. Taken together, our findings reveal the role of PirB/LILRB2 in NASH pathogenesis and identify PirB/LILRB2-ANGPTL8 signaling as a potential target for the management or treatment of NASH. Inhibition of immunocyte infiltration and activation has been suggested to ameliorate hepatic inflammation and fibrosis in nonalcoholic steatohepatitis. Here, the authors show PirB/LILRB2 regulates the migration of macrophages during NASH by binding with ANGPTL8, which is involved in the regulation of NASH development.
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影响因子：
--
作者：
Chen S;Chen J;Meng XL;Shen JS;Huang J;Huang P;Pu Z;McNeill NH;Grayburn PA
通讯作者：
Grayburn PA
影响因子：
6.7
作者：
Kazankov, Konstantin;Barrera, Francisco;Gronbaek, Henning
通讯作者：
Gronbaek, Henning
血管生成素样蛋白 8 加速 ApoE-/- 小鼠的动脉粥样硬化
影响因子：
5.3
作者：
Jiao, Xiaolu;Yang, Yunyun;Qin, Yanwen
通讯作者：
Qin, Yanwen
影响因子：
17.1
作者：
Bochner DN;Sapp RW;Adelson JD;Zhang S;Lee H;Djurisic M;Syken J;Dan Y;Shatz CJ
通讯作者：
Shatz CJ
影响因子：
17.1
作者：
Govaere, Olivier;Cockell, Simon;Anstee, Quentin M.
通讯作者：
Anstee, Quentin M.