Background: Myeloid cells, especially mononuclear phagocytes, which include monocytes, macrophages and\ndendritic cells (DC), play vital roles in innate immunity, and in the initiation and maintenance of adaptive immunity.\nWhile T cell-associated activation pathways and cytokines have been identified and evaluated in inflammatory\nbowel disease (IBD) patients (Neurath, Nat Rev Gastroenterol Hepatol 14:269â??78, 1989), the role of mononuclear\nphagocytes are less understood. Recent reports support the crucial role of DC subsets in the development of acute\ncolitis models (Arimura et al., Mucosal Immunol 10:957â??70, 2017), and suggest they may contribute to the\npathogenesis of ulcerative colitis (UC) by inducing Th1/Th2/Th17 responses (Matsuno et al., Inflamm Bowel Dis 23:\n1524â??34, 2017).\nResults: We performed in silico analysis and evaluated the enrichment of immune cells, with a focus on\nmononuclear phagocytes in IBD patient colonic biopsies. Samples were from different gut locations, with different\nlevels of disease severity, and with treatment response to current therapies. We observe enrichment of monocytes,\nM1 macrophages, activated DCs (aDCs) and plasmacytoid dendritic cells (pDCs) in inflamed tissues from various gut\nlocations. This enrichment correlates with disease severity. Additionally, the same mononuclear phagocytes subsets\nare among the top enriched cell types in both infliximab and vedolizumab treatment non-responder samples. We\nfurther investigated the enrichment of selected DC and monocyte subsets based on gene signatures derived from\na DC- and monocyte-focused single cell RNA-seq (scRNA-seq) study (Villani et al., Science 356:eaah4573, 2017), and\nverified enrichment in both inflamed tissues and those with treatment resistance. Moreover, we validated an\nincreased mononuclear phagocyte subset abundance in a Dextran Sulphate Sodium (DSS) induced colitis model in\nC57Bl/6 mice representative of chronic inflammation.\nConclusions: We conducted an extensive analysis of immune cell populations in IBD patient colonic samples and\nidentified enriched subsets of monocytes, macrophages and dendritic cells in inflamed tissues. Understanding how\nthey interact with other immune cells and other cells in the colonic microenvironment such as epithelial and\nstromal cells will help us to delineate disease pathogenesis.
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