Updated project metadata. Crohn's disease (CD) is a chronic condition characterized by recurrent flares of inflammation of the gastrointestinal tract. Despite decades of research, the etiology of CD is poorly understood and is characterized by dysregulated immune activation that progressively destroys the gastrointestinal tissue. At the center of the pathology is the intestinal mucosa, where the epithelium and the lamina propria are main cellular compartments. While the epithelium contains predominantly epithelial cells, the lamina propria is enriched in immune cells and contains supporting stroma. Thus, the cells constituting these compartments can be classified as epithelial cells, immune cells and stromal cells. Gaining insight into how these cell types interact with each other is important to further our understanding of CD pathogenesis. Here, using isobaric labeling-based quantitative proteomics, we perform an exploratory study to analyze in-depth proteome changes in epithelial cells, immune cells and stromal cells purified by cell sorting from the intestinal mucosa of CD patients and controls. Our workflow preserving the link between the different cell types in individuals opens the possibility to explore cellular crosstalk and to further refine data on cell-cell interactions in the development of CD.