IFNγ-Treated Macrophages Induce EMT through the WNT Pathway: Relevance in Crohn’s Disease

• Published in: Biomedicines Vol. 10; no. 5; p. 1093
• Main Authors: Macias-Ceja, Dulce C., Coll, Sandra, Bauset, Cristina, Seco-Cervera, Marta, Gisbert-Ferrándiz, Laura, Navarro, Francisco, Cosin-Roger, Jesus, Calatayud, Sara, Barrachina, María D., Ortiz-Masia, Dolores
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.05.2022; MDPI
• Subjects: Behavior; CD16 antigen; CD86 antigen; Cell culture; Crohn disease; Crohn's disease; Cytokines; Cytometry; Epithelial Mesenchymal Transition (EMT); Fibrosis; Flow cytometry; Genotype & phenotype; IFNγ; Inflammatory bowel disease; Interleukin 1; Interleukin 10; Interleukin 4; Intestine; Ligands; Macrophages; Mesenchyme; Microenvironments; Phenotypes; Polymerase chain reaction; Protein expression; Proteins; Signal transduction; Small intestine; Surgery; Tumor necrosis factor-α; Variance analysis; Wnt protein; γ-Interferon; Canada; Montreal Quebec Canada; United Kingdom > UK; United States > US; Madrid Spain; Spain; IFNγ; Crohn disease; macrophages; fibrosis; Epithelial Mesenchymal Transition (EMT)
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines10051093

Background: Fibrosis is a common complication of Crohn’s disease (CD) in which macrophages play a central role. Epithelial-mesenchymal transition (EMT) and the WNT pathway have been associated with fibrosis. We aim to analyse the relevance of the tissue microenvironment in macrophage phenotype and the EMT process. Methods: Intestinal surgical resections are obtained from control and CD patients with stenotic or penetrating behaviour. Cytokine’s expression, macrophage phenotype, EMT markers and WNT signalling pathway are determined by WB, RT-PCR, ELISA or Cytometry. U937 cells are treated with IFNγ, TNFα, IL1β, IL4 or IL10 and co-cultured with HT29 cells and, in some cases, are treated with XAV939 or miFZD4. The expression of macrophage, EMT and WNT pathway markers in U937 or HT29 cells is analysed by WB or RT-PCR. Results: IFNγ, WNT6, CD16 and CD86 are increased in the intestinal tissue of CD patients. IFNγ-treated U937 activated the EMT process and WNT pathway in HT29 cells, and the EMT process is mediated by FZD4. Conclusions: An IFNγ-rich microenvironment polarises macrophages, which induces EMT through the WNT pathway.