Intestinal macrophage mRNA sequencing of patients with colonic inflammatory bowel disease and a cohort of healthy controls
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ABSTRACT: The objective of this study was to investigate the role of intestinal macrophages in inflammatory bowel disease. A prospective observational study was completed. Gut biopsies from patients with Ulcerative Colitis, Crohn’s Disease and Healthy donors were harvested. Using Fluorescence-activated cell sorting a purified CD14+/CD163+ intestinal macrophage population was isolated. RNA extracted and amplified from this population of macrophages was subjected to RNA-sequencing and bioinformatically analysed. The most relevant candidates were validated with RT-qPCR and immunohistochemistry. Intestinal macrophages in UC and CD patients show a strong reprograming with over 1200 and 800 dysregulated genes, respectively. UC and CD intestinal macrophages showed an activated M1 inflammation associated to the attraction and activation of inflammatory T-cells and a Th1 immune response. Interestingly, macrophages from CD also showed a significant activation of M2 genes, associated with a Th2 response. Mirroring clinical observations, CD (but not UC) macrophages showed enrichment of expression of fibrotic and granuloma genes. Both UC and CD macrophages are down-regulating genes engaged in drug/xenobiotics metabolism roles key for IBD therapy (such as TPMT). Key genes such as MMP12 (fibrosis), CXCL9 (T-cell attraction) and CD40 (T-cell activation) were confirmed by RT-qPCR and also at the protein level by immunohistochemistry.
ORGANISM(S): Homo sapiens
PROVIDER: GSE123141 | GEO | 2021/09/20
REPOSITORIES: GEO
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