Objective Peripheral helper T (Tph) cells interact with B cells and promote immune responses at sites of ectopic lymphoid structures (ELSs). To assess the characteristics of Tph cells, we investigated the phenotype of T helper (Th) cells in patients with systemic lupus erythematosus (SLE) and the underlying competitive binding mechanisms using cytokines-mediated signal transducer and activator of transcription (STAT) factors. Methods Peripheral blood mononuclear cells from SLE patients and healthy controls were analyzed for phenotype identifying. Serum cytokine levels were detected using Luminex assays. In vitro culture was performed to assess cytokine-induced conversion of phenotypes and transcriptional regulation using flow cytometry and PCR. Chromatin immunoprecipitation was used to evaluate STATs binding and histone modifications. Results CXCR5-PD-1+Tph-like cells were increased in SLE patients and showed strong association with disease activity and renal involvement. Serum IFN-α levels were increased and associated with Tph frequency. IFN-α promoted the differentiation of IL-10-producing CXCR5-PD-1+Tph-like cells, increased the responsiveness of IL-2, and induced the conversion of Tfh-like cells to Tph-like cells. STAT5 gained advantage and bound to BCL6 locus at expense of STAT1, accompanied by suppression of H3K4me3. Finally, anti-IFNAR1 decreased the differentiation of Tph-like cells, thereby suppressing the generation of CD38highCD27highplasmablasts. Conclusion Tph cells might be crucial makers to effectively reflect disease activity level in SLE patients. The finding that synergy of IFN-α and IL-2 increases Tph cells through competitive transcriptional regulation, could be one of the mechanisms responsible for pathologic formation of ELSs and helpful for selection of individualized therapeutic approaches for SLE.

BackgroundIgAV, the most common systemic vasculitis in childhood, is an immunoglobulin A-associated immune complex-mediated disease and its underlying molecular mechanisms are not fully understood. This study attempted to identify differentially expressed genes (DEGs) and find dysregulated immune cell types in IgAV to find the underlying pathogenesis for IgAVN.MethodsGSE102114 datasets were obtained from the Gene Expression Omnibus (GEO) database to identify DEGs. Then, the protein-protein interaction (PPI) network of the DEGs was constructed using the STRING database. And key hub genes were identified by cytoHubba plug-in, performed functional enrichment analyses and followed by verification using PCR based on patient samples. Finally, the abundance of 24 immune cells were detected by Immune Cell Abundance Identifier (ImmuCellAI) to estimate the proportions and dysregulation of immune cell types within IgAVN.ResultA total of 4200 DEGs were screened in IgAVN patients compared to Health Donor, including 2004 upregulated and 2196 downregulated genes. Of the top 10 hub genes from PPI network, STAT1, TLR4, PTEN, UBB, HSPA8, ATP5B, UBA52, and CDC42 were verified significantly upregulated in more patients. Enrichment analyses indicated that hub genes were primarily enriched in Toll-like receptor (TLR) signaling pathway, nucleotide oligomerization domain (NOD)-like receptor signaling pathway, and Th17 signaling pathways. Moreover, we found a diversity of immune cells in IgAVN, consisting mainly of T cells. Finally, this study suggests that the overdifferentiation of Th2 cells, Th17 cells and Tfh cells may be involved in the occurrence and development of IgAVN.ConclusionWe screened out the key genes, pathways and maladjusted immune cells and associated with the pathogenesis of IgAVN. The unique characteristics of IgAV-infiltrating immune cell subsets were confirmed, providing new insights for future molecular targeted therapy and a direction for immunological research on IgAVN.