ILC2-derived LIF licences progress from tissue to systemic immunity In this study, researchers investigated the role of leukemia inhibitory factor (LIF), which is a cytokine produced by type 2 innate lymphocytes (ILC2), in regulating the migration of immune cells from lung tissue to lymph nodes. They performed flowcytometry analysis of immune cell changes in the lungs and lung drainage mediastinal lymph nodes after acute recombinant mouse IL-33 treatment and showed an increase in the number of plasmacytoid dendritic cells (pDCs). Using Mice with deficiency in specific immune cells they showed that ILC2s were the key factor in the increase of pDC induced by IL-33, but not T cells and B cells. Through analyzing the expression of LIF receptor (LIFR) on pDCs, they found that LIF could regulate the migration of pDCs through LIFR. Genetic knockout experiments of LIF further confirmed that LIF produced by ILC2 played an important role in the migration of pDCs to lymph nodes. Through RNA sequencing and flowcytometry, researchers showed that IL-33 treatment upregulated CCR7 expression on pDCs, while the loss of LIF led to a decrease in the number of CCR7+ pDCs in lungs and lymph nodes. In vivo study showed that LIF-deficient led to an enhanced antiviral immune response after infection, accompanied by an increased aggregation of inflammatory cells in lungs and a significant reduction in the number of immune cells in lymph nodes. This study revealed the key role of LIF produced by ILC2 in regulating the migration of immune cells from the lungs to the lymph nodes, thereby maintaining a balance between local tissue immunity and systemic immunity. DOI: 10.1038/s41586-024-07746-w
Myeloid beta-arrestin 2 depletion attenuates metabolic dysfunction-associated steatohepatitis via the metabolic reprogramming of macrophages![]()
Xiaoli Wei et al.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health problem, with metabolic dysfunction-associated steatohepatitis (MASH) as a more severe form. As the most abundant innate immune cells in the liver, macrophages phenotype transformation plays important roles in the onset of MASLD/MASH. In this study, using β-arrestin 2 systemic and myeloid specific knockout mice, as well as three dietary models of high fat diet (HFD), high fat high cholesterol (HFHC), and methionine choline deficiency (MCD), the authors found that myeloid specific β-arrestin 2 was a key protein in maintaining the proinflammatory phenotype of liver macrophages and promoting the progression of MASH in mice. In the liver, β-arrestin 2 was mainly expressed in macrophages, and the expression of β-arrestin 2 in human and mouse liver macrophages was significantly increased in MASLD. Myeloid-specific β-arrestin 2 depletion reduced liver inflammation and fibrosis in MASH mice. The absence of β-arrestin 2 could promote the production of itaconic acid in liver macrophages and inhibit the M1-type polarization of macrophages. These results suggested the role and mechanism of myeloid β-arrestin 2 in MASH, providing new targets and ideas for prevention and intervention of MASH.
DOI: 10.1016/j.cmet.2024.08.010
Editor & Reviewer: Yanwen Wang
