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MyD88 regulates the function of polymorphonuclear myeloid-derived suppressor cells in experimental autoimmune encephalomyelitis 2774

Year: 2025
Type: article
Abstract: Description Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid lineage cells with potent immunosuppressive properties. The role of MDSCs in autoimmune diseases such as multiple sclerosis (MS) is controversial, with limited studies exploring the molecular mechanisms regulating MDSC function. In this study, we observed an expansion of polymorphonuclear (PMN)-MDSCs in both patients with MS and its animal model, experimental autoimmune encephalomyelitis (EAE). These expanded PMN-MDSCs in EAE mice suppressed CD4+ T cell proliferation but promoted Th17 cell differentiation in vitro. Transcriptome analysis revealed increased expression of “MDSC-marker genes”, further confirming their identity as PMN-MDSCs. To explore the molecular mechanisms regulating PMN-MDSC functions, we performed a protein-protein interaction network analysis and identified myeloid differentiation primary response 88 (MyD88) as a central hub gene. Notably, PMN-MDSCs from MS patients also exhibited elevated expression of MYD88. Next, we assessed the impact of MyD88 deficiency on PMN-MDSC functions in EAE. Significantly, MyD88-deficient PMN-MDSC exhibited impaired suppressive function, reduced ability to promote Th17 cell differentiation, and compromised migratory capacity. In conclusion, these findings highlight the crucial regulatory role of MyD88 in modulating PMN-MDSC functions in EAE, providing a potential target for immunotherapy in autoimmune diseases like MS. Funding Sources This work is supported by the National Natural Science Foundation of China (82371350) Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)
DOI: 10.1093/jimmun/vkaf283.657
Language: English
Subfield: Immunology
Open Access status: bronze
OpenAlex ID: W4416446612
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