LILRB2/PirB mediates macrophage recruitment in fibrogenesis of nonalcoholic steatohepatitis

Autor: 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, De-Lin Ma, Ben-Ping Zhang, Shi-Ying Shao, Xi Chen, Si-Miao Xu, Wen-Tao He, Wen-Jun Li, Yong Chen, Xue-Feng Yu
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Nature Communications, Vol 14, Iss 1, Pp 1-17 (2023)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-023-40183-3
Popis: 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.
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