LILRB2/PirB mediates macrophage recruitment in fibrogenesis of nonalcoholic steatohepatitis

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.

LbSakA‐mediated phosphorylation of the scaffolding protein LbNoxR in the ectomycorrhizal basidiomycete Laccaria bicolor regulates NADPH oxidase activity, ROS accumulation and symbiosis development

“…The activation of SakA has been demonstrated to be mediated by phosphorylation (Mosbacher et al ., 2023). The alkaloids dehydrocorydaline chloride (DHC, 13‐Methylpalmatine chloride) and SB203580 (Adezmapimod) are commonly used activators and inhibitor of P38 mitogen‐activated protein (MAP) kinase, respectively, and exert opposing effects on the phosphorylation of SakA (Li et al ., 2023; Liu et al ., 2023). To elucidate the physiological function of LbSakA, a range of concentrations of DHC and SB203580 was tested in the WT strain to establish the optimal conditions for its activity (Fig.…”

Identification of shared pathogenetic mechanisms between COVID-19 and IC through bioinformatics and system biology

“…Furthermore, utilizing the four methods of the CytoHubba plugin, we identified a total of seven hub genes. LILRB2, in combination with ANGPTL8, can enhance the migration and inflammatory activation of monocyte-derived macrophages 50 . After being cleaved by caspases, MNDA builds up in the cytoplasm, aiding in the breakdown of the antiapoptotic protein Mcl-1 and encouraging neutrophil apoptosis 51 .…”