LILRB2/PirB mediates macrophage recruitment in fibrogenesis of nonalcoholic steatohepatitis

Dan-Pei Li, Li Huang, Ran-Ran Kan, Xiao-Yu Meng, Shu-Yun Wang, Hua-Jie Zou, Ya-Ming Guo, Pei-Qiong Luo, Li-Meng Pan, Yu-Xi Xiang, Bei-Bei Mao, Yu-Yu Xie, Zhi-Han Wang, Min Yang, Rui He, Yan Yang, Zhe-Long Liu, Jun-Hui Xie, Ma De-Lin, Ben-Ping Zhang, Shi-Ying Shao, Xi Chen, Si-Miao Xu, Wen-Tao He, Wen-Jun Li, Yong Chen () and Xue-Feng Yu ()
Additional contact information
Dan-Pei Li: Huazhong University of Science and Technology
Li Huang: Huazhong University of Science and Technology
Ran-Ran Kan: Huazhong University of Science and Technology
Xiao-Yu Meng: Huazhong University of Science and Technology
Shu-Yun Wang: Huazhong University of Science and Technology
Hua-Jie Zou: Huazhong University of Science and Technology
Ya-Ming Guo: Huazhong University of Science and Technology
Pei-Qiong Luo: Huazhong University of Science and Technology
Li-Meng Pan: Huazhong University of Science and Technology
Yu-Xi Xiang: Huazhong University of Science and Technology
Bei-Bei Mao: Huazhong University of Science and Technology
Yu-Yu Xie: Huazhong University of Science and Technology
Zhi-Han Wang: Huazhong University of Science and Technology
Min Yang: Huazhong University of Science and Technology
Rui He: Huazhong University of Science and Technology
Yan Yang: Huazhong University of Science and Technology
Zhe-Long Liu: Huazhong University of Science and Technology
Jun-Hui Xie: Huazhong University of Science and Technology
Ma De-Lin: Huazhong University of Science and Technology
Ben-Ping Zhang: Huazhong University of Science and Technology
Shi-Ying Shao: Huazhong University of Science and Technology
Xi Chen: Huazhong University of Science and Technology
Si-Miao Xu: Huazhong University of Science and Technology
Wen-Tao He: Huazhong University of Science and Technology
Wen-Jun Li: Huazhong University of Science and Technology
Yong Chen: Huazhong University of Science and Technology
Xue-Feng Yu: Huazhong University of Science and Technology

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-40183-3

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