Relationship between human intestinal dendritic cells, gut microbiota, and disease activity in Crohnʼs disease

Abstract

IL-6 production by intestinal DC is increased in CD and correlates with disease activity and CRP. Bacterially driven local IL-6 production by intestinal DC may overcome regulatory activity, resulting in unopposed effector function and tissue damage. Intestinal DC function may be influenced by the composition of the commensal microbiota.

T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

“…Links between bacterial infections and autoimmune diseases of the gut have been found [98,99]. However, the complexity of the human microbiome may make it difficult to deconvolute the many cross-reactive peptides that could be driving this link.…”

Characterization of the Gastrointestinal Microbiota in Health and Inflammatory Bowel Disease

“…115 It has recently been shown that IL-6 production by intestinal DCs is increased in CD and correlates with disease activity and C-reactive protein, and intestinal DC function may be influenced by the composition of the commensal microbiota. 116 Commensal microbiota, such as Bacteroides fragilis, express molecules such as polysaccharide A which protect against the proinflammatory effects of potentially pathogenic microbiota by stimulating IL-10-producing CD4þ T cells. [117][118][119] Similarly, the commensal Fecalibacterium prausnitzii has been shown to have antiinflammatory effects due to secreted metabolites which block NF-jB activation and IL-8 production.…”

Intestinal dendritic cell and macrophage subsets: Tipping the balance to Crohn's Disease?

“…In general, studies have shown an increase in both DC and macrophage populations in the intestinal lamina propria in Crohn's Disease patients [20,32,33,[50][51][52]. Studies have also consistently shown that DCs in Crohn's Disease are more activated and have higher expression of microbial recognition receptors, particularly TLR4 [8,27,50,53,54]. These findings support intestinal phagocytes as likely key mediators of the pro-inflammatory response.…”

“…However, it has been shown that IL-6 and IL-12 are over-produced by DCs from Crohn's Disease patients [53]. Consistent with this, Ng et al [54] showed that DCs from patients with Crohn's Disease express more IL-12p40 and IL6 compared to healthy controls. Finally, LPS stimulation of mucosal DCs in Crohn's Disease patients induced high secretion of TNFα and IL-8 [35].…”