MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages
Cell Mol Immunol. 2023 Oct 13. doi: 10.1038/s41423-023-01089-8. Online ahead of print.ABSTRACTPrimary immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder in which macrophages play a critical role. Mammalian sterile-20-like kinase 4 (MST4), a member of the germinal-center kinase STE20 family, has been demonstrated to be a regulator of inflammation. Whether MST4 participates in the macrophage-dependent inflammation of ITP remains elusive. The expression and function of MST4 in macrophages of ITP patients and THP-1 cells, and of a macrophage-specific Mst4-/- (Mst4ΔM/ΔM) ITP mouse model were determined. Macrophage phagocytic assays, RNA sequencing (RNA-seq) analysis, immunofluorescence analysis, coimmunoprecipitation (co-IP), mass spectrometry (MS), bioinformatics analysis, and phosphoproteomics analysis were performed to reveal the underlying mechanisms. The expression levels of the MST4 gene were elevated in the expanded M1-like macrophages of ITP patients, and this elevated expression of MST4 was restored to basal levels in patients with remission after high-dose dexamethasone treatment. The expression of the MST4 gene was significantly elevated in THP-1-derived M1 macrophages. Silencing of MST4 decreased the expression of M1 macrophage markers and cytokines, and impaired phagocytosis, which could be increased by overexpression of MST4. In a passive ITP mouse model, macrophage-specific depletion of Mst4 reduced the numbers of M1 macrophages in the spleen and ...
Source: Cellular and Molecular Immunology - Category: Molecular Biology Authors: Jingjing Cao Lili Ji Yanxia Zhan Xia Shao Pengcheng Xu Boting Wu Pu Chen Luya Cheng Xibing Zhuang Yang Ou Fanli Hua Lihua Sun Feng Li Hao Chen Zhaocai Zhou Yunfeng Cheng Source Type: research
More News: Allergy & Immunology | Dexamethasone | Genetics | Molecular Biology | Pathology | Study | Thrombocytopenia