Lupus Erythematosus, Systemic study with ATAC-seq, RNA-Seq data on dbGaP (38 participants)

phs003582 — Regulation of T Cell CXCL13 Production

This study evaluated the signals that regulate production of the B cell chemoattractant <a href="https://www.ncbi.nlm.nih.gov/gene/10563">CXCL13</a> by human CD4 T cells. Single-cell and bulk RNA-seq datasets evaluated the gene expression changes induced by TGF-beta and the aryl hydrocarbon receptor (<a href="https://www.ncbi.nlm.nih.gov/gene/196">AHR</a>), two signals that regulate CXCL13 production. Bulk ATAC-seq data evaluated the epigenetic changes in T cell stimulated with an AHR agonist or antagonist. Ex vivo bulk RNA-seq data of sorted T cell subsets from blood of patients with lupus and control donors interrogated the gene expression differences in sorted T cell subsets. Ex vivo ATAC-seq data allowed comparison of epigenetic profiles of <a href="https://www.ncbi.nlm.nih.gov/gene/5133">PD-1</a>hi Tph cells from rheumatoid arthritis synovial fluid and PD-1hi T follicular helper (Tfh) cells from tonsil to PD-1low <a href="https://www.ncbi.nlm.nih.gov/gene/920">CD4</a> T cells from the same samples. Single-cell RNA-seq data of T cells from lupus patients before and after treatment with anifrolumab (anti-IFNAR) allowed interrogation of T cell populations that change with anifrolumab treatment. These datasets allowed for genomic interrogation of changes induced by AHR, TGF-beta, and interferon and their relationship to CXCL13 production.