Interleukin-33 driven mesenchymal stromal cells suppress group 2 innate lymphoid cell proliferation in Endometriosis 3398

Abstract Description Introduction Interleukin-33 (IL-33) driven group 2 innate lymphoid cells (ILC2) perpetuate cardinal features of endometriosis (EM)- inflammation, fibrosis, vascularization. Mesenchymal stromal cells (MSC) are primary sources of IL-33 and have been shown to modulate ILC2 function. In this study, we address the interplay between ILC2s and MSCs to understand the critical role of the IL-33/MSC/ILC2 axis in shaping the EM lesion microenvironment. Methods Mice (C57Bl6) with or without EM surgical induction were treated intraperitoneally every other day with IL-33 (3 injections in 1 week). ILC2s and MSCs were cultured following isolation from cell suspensions of EM associated tissues (peritoneal lavage, uterus, lesion) using magnetic enrichment and FACS (viability, CD45). Culture supernatant was analyzed for multiplex cytokine array and cells utilized for bulk RNA sequencing. Results ILC2s cultured alone proliferated significantly more than ILC2s cultured with MSCs, highlighting a suppressive MSC/ILC2 crosstalk. Supernatant collected from co-cultures had significantly higher levels of chemokines (G-CSF, MCP-1, eotaxin) and VEGF, relevant to EM lesion maintenance, compared to ILC2s cultured alone. This suggests ILC2/MSC may work in concert to drive EM associated inflammation and tissue remodeling. Conclusion Preliminary evidence suggests that MSCs regulate ILC2 function. On-going experiments will provide insights as to how ILC2/MSC interactions contribute to EM pathophysiology. Funding Sources Supported by Canadian Institutes of Health Research (394022) Topic Categories Immune Mechanisms of Human Disease (HUM)