Identifying potential mechanism and targets for treatment of tertiary lymphoid structure in lupus nephritis based on bioinformatics analysis

Tertiary lymphoid structure (TLS) is an ectopic lymphoid structure that develops in non-lymphoid structures. Some studies have shown that the TLS formed in autoimmune diseases, such as lupus nephropathy (LN), can cause damage to normal tissues and continuous disease progression. Nevertheless, there is still a lack of efficient treatments for TLS in LN. Thus, the study aims to identify potential targets for therapy of TLS in LN. Mice datasets relative to TLS were obtained from Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified from mice datasets. Then, the Genetic Ontological (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed. The Protein-Protein Interaction (PPI) network was constructed. Additionally, the hub genes were selected by Cytoscape and verified by human databases from GEO. The relationships between the immune cells with hub genes were explored. Finally, the two genes PSMB9 and STAT1 were validated in the kidney tissues of LN patients and mice. 443 DEGs and 178 DEGs relative to TLS were filtered from GSE160488 and GSE155405, respectively. The enrichment results of these genes mostly focused on inflammatory response, cytokine-cytokine receptor interaction, and immune system process. Six genes were recognized by Cytoscape. According to the validation of six genes in human databases, the two hub genes (PSMB9 and STAT1) were also significantly expressed in LN patients. Immune infiltration analysis of hub genes shows immune cells are significantly crucial in LN patients with TLS. PSMB9 and STAT1 may be identified as possible targets for the treatment of TLS in LN. According to the analysis of the interaction between these genes and immune cells, the immune process mediated by these signature targets takes part in the advancement and formation of TLS.