New Insights into Roles of IL-7R Gene as a Therapeutic Target Following Intracerebral Hemorrhage.

Abstract

Spontaneous intracerebral hemorrhage (ICH) is a subtype of stroke leading to high rates of morbidity and mortality in adults. Recent studies showed that immune and inflammatory responses might play essential roles in secondary brain injury. The purpose of this article was to provide a reference for further therapeutic strategies for ICH patients. GSE206971 and GSE216607 datasets from the gene expression omnibus (GEO) database were used to screen the highly immune-related differentally expressed genes (IRDEGs). We used the CIBERSORT algorithm to assess the level of immune signatures infiltration and got the possible function of IRDEGs which was analyzed through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Protein-protein interaction (PPI) networks and six hub genes were identified in the Cytoscape plug-in. GSVA algorithm was performed to evaluate the potential pathways of six hub genes in ICH samples. The expression level of IL-7R chosen from six hub genes was further validated by Western blotting. The cell models of ICH were established for the research of IL-7/IL-7R signaling way. A total of six hub genes (ITGAX, ITGAM, CCR2, CD28, SELL, and IL-7R) were identified. IL-7R was highly expressed in the mice ICH group, as shown by immunoblotting. Next, we constructed ICH cell models in RAW264.7 cells and BV2 cells. After treatment with IL-7, iNOS expression (M1 marker) was greatly inhibited while Arg-1(M2 marker) was enhanced, and it might function via the JAK3/STAT5 signaling pathway. The hypothesis is proposed that the IL-7/IL-7R signaling pathway might regulate the inflammatory process following ICH by regulating microglia polarization. Our study is limited and requires more in-depth experimental confirmation.