Ligand-receptor mapping via RNA of Crohn’s disease inflammation reveals spatial variation in monocyte and macrophage activity 9316

Abstract Description Inflammatory bowel disease (IBD) is an autoinflammatory condition affecting millions of people globally. Most IBD cases can be categorized as ulcerative colitis or Crohn’s disease. Both result in chronic inflammatory pathology leading to pain, impaired digestive function, and poor quality of life. Life-threatening complications can also occur, such as ileal strictures in Crohn’s disease. Inflammatory monocytes and macrophages have recently emerged as a key cell type in IBD. Multiple studies have established their correlation to disease pathology and their persistence in individuals failing frontline TNF-inhibitor therapy. These cells are well-positioned to encode and perpetuate disease activity due to their ability to sense innate signals and to drive lymphocyte activation. However, while their abundance and transcriptomic profiles have been studied, there is relatively little information as to their spatial localization and cellular neighborhoods in IBD. We leverage spatial transcriptomics with subcellular resolution and a 5000 gene panel to interrogate immune inter-cellular communication between inflammatory associated monocytes and macrophages and their surrounding cellular cohort within a Crohn’s disease stricturing terminal ileum. Using a full-thickness gut biopsy we map the colocalization of significant ligand receptor pairs, where we find evidence to support known pro-inflammatory activity, and potentially novel cell-cell crosstalk. Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)