Increased Production of Retinoic Acid by Intestinal Macrophages Contributes to Their Inflammatory Phenotype in Patients With Crohn's Disease

Azathioprine therapy selectively ablates human Vδ2+ T cells in Crohn’s disease

“…Intestinal antigen-presenting cells (APCs) metabolize dietary vitamin A into retinoic acid (RA), which exerts potent effects on T cell differentiation, effector function, gut tropism, and migration to inflamed tissues (29)(30)(31). Having recently reported that human intestinal APC display increased capacity for RA synthesis in inflammatory bowel disease (IBD) (32), and that human Vδ2 T cell function can be modified by exposure to RA in vitro (11), we hypothesized that RA signaling might influence Vδ2 T cell production of proinflammatory mediators in the CD intestine in vivo. To test this hypothesis, we collected biopsies of inflamed colonic mucosa from patients with new diagnoses of CD and assessed tissue were relatively poor cytokine producers (11).…”

Diversity and functions of intestinal mononuclear phagocytes

“…85,107,118,[202][203][204][205] However many phenotypic markers of the myeloid lineage including CD11b, F4/80 and CD11c…”

“…5 CD163 or CD206 are also expressed by most mature m in humans, but they express low amounts of CD14, which is found at high levels on classical monocytes and immature m . 85,107,118,[202][203][204][205] Using markers of this kind, it can be shown that a monocyte-m "waterfall" 142 Indeed, there appear to be several differences in how responsiveness to pattern recognition receptors is regulated in human and murine m in general. 206 As in mice however, IL-10 plays an essential role in controlling the pro-inflammatory potential of human intestinal m and non-functional mutations in the IL-10R lead to severe, early onset IBD.…”

“…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.…”

“…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. 85 Interestingly, autocrine signalling via the RA receptor has been suggested to contribute to the production of TNF by m . Finally, although there is much reduced recruitment of monocytes to the colon of germ free mice compared with conventionally housed controls, 115 mature m remain present in germ free colon, indicating the microbiota does not play an essential role in their development.…”