Regulation of Interleukin-23 Receptor expression in human T-Lymphocytes

Chronic inflammatory diseases (CID) are clinically heterogeneous conditions that share common inflammatory pathways and derive from aberrant immune responses. Genome-wide association studies (GWAS), together with mouse models of autoimmune disease, demonstrated that Th17 cells play a pivotal role in the initiation of these diseases. The implication of the IL-23/IL-17 axis in several CID is supported by the finding that several of the non-MHC loci genetically linked to Crohn’s disease, psoriasis, and axial spondyloarthritis (axSpA), are associated with genes in this pathway. It’s known that IL-23 is important for the expansion and the functional activity of the Th17 cell subset. However, several studies have suggested that IL-23 may also regulate the function of IL-17-producing innate immune cells, which express the IL-23 receptor (IL-23R). Indeed, substantially less is known about the biologic function of IL-23 in human inflammatory disease, although GWAS results have pointed to an important role of IL23R in the pathogenesis of several CID, while the mechanism controlling the expression of this gene in different lymphocyte populations are poorly understood. The goal of this study is to increase our knowledge of the role of IL-23 and the signals necessary to induce IL23R expression in neonatal CD4+ T cells or whether environmental signals are required to induce its expression in these innate T cell populations. To address the molecular mechanisms of IL23R induction, we will identify regions with an open chromatin conformation (which are often regulatory elements) in the IL23R locus, in adaptive and innate T cell populations (CD4+ CCR6+ and CD8+ CCR6+ T cells) using ATAC-seq, which requires low cell numbers. Through bioinformatic analysis and literature research we aim to define the putative transcription factors with their binding sites, and research a possible molecular mechanisms controlling IL23R expression in CD4+ T cells exploiting TF knock-down by siRNA technology.