Gene-gene interaction networks for SYK in immune cell subsets for allergies and asthma

<bold>Introduction:</bold> Prior research revealed a 51-gene transcript set that may be hallmark genes that are affected by cytokines (e.g., IL-3) in human basophils. We hypothesize that peripheral blood basophils (PBBs) may respond to stimuli by expressing distinct transcriptome signatures, which may be used to identify basophil phenotypes linked to asthma and allergy reactions in humans. <bold>Methods:</bold> We utilized the STRING database to explore the gene-gene interaction networks derived from signature genes in PBBs in response to cytokines. To investigate the expression patterns for these associated genes among specific immune cell types, we utilized the expression data produced by single-cell RNA sequencing (scRNA-seq) in the sc-eQTLGen Consortium. <bold>Results:</bold> We observed interactions for 26 out of the 51-gene transcript set. Further clustering analysis identified 8 key genes (CCL3, CCL5, FCGR2A, FCGR2B, IL1B, IL2RB, GZMB, and SOCS1) that directly interact with SYK, an important component of the IgE-mediated reaction. Using PBMCs from 45 donors, we then investigated the expression patterns of associated genes. In PBMCs stimulated with P. aeruginosa for 3 hours compared to untreated samples, we observed significantly higher expression of SYK in monocytes, DCs, B cells and progenitors (p<0.05). This trend is consistent with our earlier findings. IL1B, CCL3, and FCGR2A are among the other key genes that were markedly overexpressed in monocytes. <bold>Conclusions:</bold> We verified that the regulation of SYK and associated molecules' gene expression is context-specific. Further studies are needed for elucidating the contribution of genetic and immune characterizations of SYK in immune cell subsets to allergic disease.