Isobaric labeling‐based quantitative proteomics of FACS‐purified immune cells and epithelial cells from the intestine of Crohn's disease patients reveals proteome changes of potential importance in disease pathogenesis. Issue 5 (25th December 2022)

• Record Type: Journal Article
• Authors: Alfredsson, Johannes; Fabrik, Ivo; Gorreja, Frida; Caër, Charles; Sihlbom, Carina; Block, Mattias; Börjesson, Lars G.; Lindskog, Elinor Bexe; Wick, Mary Jo
• Is Part Of: Proteomics. Volume 23:Issue 5(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-25
• Subjects: Cell sorting -- Epithelial cells -- Immune Cells -- Intestinal inflammation -- TMT labeling; Proteins -- Separation -- Periodicals; Bioinformatics -- Periodicals; Proteomics -- Periodicals; Genomes -- Periodicals; Molecular genetics -- Periodicals; 572.605
• DOI: 10.1002/pmic.202200366
• Languages: English
• ISSNs: 1615-9853

Abstract

Abstract: Crohn's disease (CD) is a chronic condition characterized by recurrent flares of inflammation in the gastrointestinal tract. Disease etiology is poorly understood and is characterized by dysregulated immune activation that progressively destroys intestinal tissue. Key cellular compartments in disease pathogenesis are the intestinal epithelial layer and its underlying lamina propria. While the epithelium contains predominantly epithelial cells, the lamina propria is enriched in immune cells. Deciphering proteome changes in different cell populations is important to understand 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 in CD patients compared to controls using cells purified by FACS. Our study revealed increased proteins associated with neutrophil degranulation and mitochondrial metabolism in immune cells of CD intestinal mucosa. We also found upregulation of proteins involved in glycosylation and secretory pathways in epithelial cells of CD patients, while proteins involved in mitochondrial metabolism were reduced. The distinct alterations in protein levels in immune‐ versus epithelial cells underscores the utility of proteome analysis of defined cell types. Moreover, our workflow allowing concomitant assessment of cell‐type specific changes on an individual basis enables deeper insight into disease pathogenesis.