An investigation of the IL-23/Th17 axis and transcriptomic profiles of Th1, Th1/17, and Th17 cells in endometriosis patients as compared to controls 3189

Abstract Description Endometriosis (EM) is an inflammatory disease driven by immune dysfunction. IL-23 is a key contributor driving IL-17-producing T-helper (Th)17 cells towards a pathogenic phenotype. IL-17 and Th17 cells are elevated and linked to EM severity. Though, mechanisms by which IL-23/mediators contribute to pathogenic Th17 profile and exacerbate EM is unknown. We seek to establish transcriptomic signatures of Th1, Th1/17, and Th17 cell subsets isolated from peripheral blood of EM patients and controls. Bulk RNA sequencing is in progress to investigate transcriptional profiles of these cell subsets. Results will be integrated with RNA transcriptome from patient eutopic and ectopic tissues. Using high-parameter flow cytometry, expression of markers distinguishing pathogenic and non-pathogenic Th17 cells will be assessed in patient peritoneal fluid (PF). Relevant cytokines in IL-23/Th17 axis were measured via multiplex cytokine array in patient PF, plasma (patients and controls), and protein extracts isolated from patient tissues. Preliminary results reveal significant dysregulation of IL-23/Th17 axis in EM. RNA sequencing and associated analyses will reveal interplay between Th1 and Th17 cell subsets and integration with immune phenotyping of PF will reflect local immune microenvironment, directly influencing EM lesion survival. This work may provide a promising therapeutic avenue to reduce the burden of EM, as IL-23 therapeutics are currently in use for various inflammatory diseases. Funding Sources This research is supported with funds from the Canadian Institutes of Health Research (CIHR 394570, CT and CIHR CGS-D 187578, DS). Topic Categories Immune Mechanisms of Human Disease (HUM)