Macrophage and dendritic cell subsets in IBD: ALDH+ cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation

Abstract

Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn’s ileitis, Crohn’s colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased CD14+DRint MQs characterized inflamed intestinal mucosa while total CD141+ or CD1c+ DCs numbers were unchanged. However, CD103+ DCs, including CD141+CD103+ and CD1c+CD103+ DCs, were reduced in inflamed intestine. In MLNs, two CD14− DC populations were identified: CD11cintHLADRhi and CD11chiHLADRint cells. A marked increase of CD11chiHLADRint DC, particularly DRintCD1c+ DCs, characterized MLNs draining inflamed intestine. The fraction of DC and MQ populations expressing aldehyde dehydrogenase (ALDH) activity, reflecting retinoic acid synthesis, in UC colon, both in active disease and remission, were reduced compared to controls and inflamed Crohn’s colon. In contrast, no difference in the frequency of ALDH+ cells among blood precursors was detected between UC patients in remission and non-inflamed controls. This suggests that ALDH activity in myeloid cells in the colon of UC patients, regardless of whether the disease is active or in remission, is influenced by the intestinal environment.

Colonic macrophage polarization in homeostasis, inflammation, and cancer

“…Thiesen and colleagues (97) have shown a marked increase in CD14 ϩ HLA-DR dim macrophages in inflamed intestinal tissue from CD patients compared with non-inflamed tissue from CD and control patients, and these macrophages were similar to proinflammatory monocytes. Magnusson and colleagues (54) have recently confirmed these results, also finding a significant increase in CD14 ϩ HLA-DR dim macrophages in inflamed colonic tissue from CD compared with noninflamed colon from these same patients or noninflamed colon from non-IBD controls. The similarity between these macrophages and proinflammatory monocytes is reminiscent of the P1 and P2 proinflammatory macrophage subsets from the developmental series described for colonic macrophages in the mouse (7,96).…”

“…Diseased areas of human UC colon biopsies contain elevated levels of CD14 ϩ HLA-DR ϩ CD64 ϩ macrophages (96). Magnusson and colleagues (54) found that CD14…”

Diversity and functions of intestinal mononuclear phagocytes

“…84,85,107,175,[207][208][209] Furthermore, these immature cells are responsible for producing large amounts of the pro-inflammatory mediators that typify these disorders, including TNF , IL-1, IL-18, IL-23, nitric oxide (NO) and reactive oxygen intermediates (ROI). 128,202,203,207,210,211 Production of RA by infiltrating monocytes and m may also be enhanced during IBD, perhaps secondary to increased levels of GM-CSF.…”

Galectin-9 Produced by Intestinal Epithelial Cells Enhances Aldehyde Dehydrogenase Activity in Dendritic Cells in a PI3K- and p38-Dependent Manner

“…In IBD, IEC do not promote the differentiation of tolerogenic DC, and, consequently, a reduction in ALDH-positive DC is observed in the lamina propria [21] . It has been demonstrated that the gut microbiota may play an important role in the recruitment of CD103 + DC towards the intestinal epithelium via TLR-dependent mechanisms [22] but, to our knowledge, it is not known whether epithelial TLR activation also regulates the differentiation of CD103 + DC.…”