The mannose receptor (CD206) identifies a population of colonic macrophages in health and inflammatory bowel disease
Pamela Wright, Elizabeth S. McDonald, Alberto Bravo‐Blas, Hannah M. Baer, Anna Heawood, Calum C. Bain, Allan McI. Mowat, Slater L. Clay, Elaine V. Robertson, Fraser Morton, Jagtar Singh Nijjar, Umer Zeeshan Ijaz, Simon Milling, Daniel R. Gaya
Abstract
Abstract To understand the contribution of mononuclear phagocytes (MNP), which include monocyte-derived intestinal macrophages, to the pathogenesis of inflammatory bowel disease (IBD), it is necessary to identify functionally-different MNP populations. We aimed to characterise intestinal macrophage populations in patients with IBD. We developed 12-parameter flow cytometry protocols to identify and human intestinal MNPs. We used these protocols to purify and characterize colonic macrophages from colonic tissue from patients with Crohn’s disease (CD), ulcerative colitis (UC), or non-inflamed controls, in a cross-sectional study. We identify macrophage populations (CD45 + CD64 + HLA-DR + ) and describe two distinct subsets, differentiated by their expression of the mannose receptor, CD206. CD206 + macrophages expressed markers consistent with a mature phenotype: high levels of CD68 and CD163, higher transcription of IL-10 and lower expression of TREM1. CD206 − macrophages appear to be less mature, with features more similar to their monocytic precursors. We identified and purified macrophage populations from human colon. These appear to be derived from a monocytic precursor with high CCR2 and low CD206 expression. As these cells mature, they 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.