The mannose receptor (CD206) identifies a population of colonic macrophages in health and inflammatory bowel disease

Pamela B Wright,Alberto Bravo-Blas,Fraser Morton,Daniel R Gaya,Slater L Clay,Umer Z Ijaz,Jagtar Singh Nijjar,Hannah M Baer,Elizabeth Mcdonald,Anna Heawood,Simon W F Milling,Calum C Bain,Allan M Mowat,Elaine V Robertson

doi:10.1038/s41598-021-98611-7

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.

Highlights

The incidence of inflammatory bowel disease (IBD) is increasing[1] and around 1 in 200 adults are affected
Much progress has already been made in identifying dendritic cells (DCs) populations in the human intestine[12,13,14,15,16,17], we focused on intestinal macrophage populations
A step-wise increase in the mannose receptor, CD206 can be seen in murine macrophages during their maturation, which we hypothesised would occur in human intestinal macrophages

Summary

Introduction

The incidence of inflammatory bowel disease (IBD) is increasing[1] and around 1 in 200 adults are affected. Aberrant MNP functions have been reported to contribute to IBD, including alterations Despite their importance, differential identification of the various MNP populations has been challenging because of the significant overlaps in their surface marker expression, and has generated much c ontroversy[8]. Recent detailed descriptions of murine MNP populations have enabled clearer identification of these cells in samples from human tissue, including s kin[18], liver, lung, b lood[19] and lymph nodes[20] Based on these findings the mannose receptor CD206 protein has been identified on macrophage populations in mice and humans, For example, in synovial tissue samples from patients with rheumatoid arthritis (RA), CD206pos and CD206neg macrophages appear to play different roles in driving inflammation or promoting tissue repair[21], and are considered to be important therapeutic t argets[22]. Targeting these newly recruited cells may be a viable strategy for controlling intestinal inflammation

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