GSE124350
Expression of the mannose receptor (CD206) defines distinct populations of human colonic macrophages in health and inflammatory bowel disease
BACKGROUND & AIMS: Intestinal mononuclear phagocytes (MNP) are phenotypically similar, but have different functions. Macrophages contribute to the pathogenesis of inflammatory bowel disease (IBD). To understand this contribution it is necessary to distinguish macrophages from other MNPs, and identify functionally-different macrophage populations. We aimed to accurately identify intestinal macrophage populations, and to ascertain their functions in patients with inflammatory bowel disease (IBD). METHODS: We developed 12-parameter flow cytometry protocols to identify and characterise human intestinal MNPs. We then used RNA sequencing, qPCR, and flow cytometry to analyse colonic biopsies from patients with CD, UC, or non-inflamed controls, in a cross-sectional study. RESULTS: We unambiguously differentiate macrophage populations (CD45+CD64+ HLA-DR+) from dendritic cells (CD45+CD64- HLA-DR+ CD11c;). We identify two distinct subsets within the macrophage population, differentiated by their expression of the mannose receptor, CD206. Further examination of these macrophage sub-populations showed that CD206+ macrophages expressed markers consistent with a mature macrophage phenotype: high levels of CD68 and CD163, higher transcription of IL-10 and lower expression of Trem1. On the contrary, CD64+ HLA-DR- CD206- cells appear to be semi-mature intermediaries in the development of mature intestinal macrophages from their monocyte precursors. CONCLUSIONS: We identified and purified MNP and macrophage populations from human intestinal lamina propria. Thorough characterisation reveals that human colonic macrophages appear to be derived from a monocytic precursor with high CCR2 and low CD206 expression. As these cells mature they lose their proliferative properties and acquire expression of IL-10, CD206, CD63, and CD168. Targeting the newly recruited monocyte-derived cells may represent a fruitful avenue to ameliorate chronic inflammation in IBD. Overall design: Examination of human colonic macrophages based on their CD206 expression. 15 samples analysed, divided between CD206+ (n=7) and CD206- (n=8)