Epithelia mediate inflammation with myeloid cells in Crohn's disease patients under treatment

Crohn's disease, a major class of Inflammatory bowel disease, is a chronic condition affecting millions, with >50% of the patients experiencing relapses marked by inflammation. Our cellular atlas (380,000 cells) of the terminal ileum and ascending colon mucosa from 46 Crohns' disease patients and non-disease donors across various clinical condition, decipher disease heterogeneity for Crohn's disease recurrent and refractory inflammation. We identified an inflammatory cascade mediated by follicle-associated enterocytes in the inflamed terminal ileum, involving pro-inflammatory macrophage M1 that remained unresolved by given biological treatments. Spatial transcriptomic validation confirmed this epithelial-immune crosstalk. In contrast, interactions between colonocytes, FAP+ stroma and innate immune cells were the unresolved cascade in AC driving inflammation. In addition, we proposed a transcript-based scoring method to quantify inflammation activity that can be used to compare inflammation levels across patients, with the overall aim to help disease stratification.