Involvement of Dendritic Cells in the Pathogenesis of Inflammatory Bowel Disease

2006 ◽  
pp. 117-132 ◽  
Author(s):  
Francisco Leon ◽  
Lesley E. Smythies ◽  
Phillip D. Smith ◽  
Brian L. Kelsall
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
Bowel Disease ◽  
Inflammatory Bowel

scholarly journals IL-10 signaling in dendritic cells controls IL-1β-mediated IFNγ secretion by human CD4+ T cells: relevance to inflammatory bowel disease

2019 ◽  
Vol 12 (5) ◽  
pp. 1201-1211 ◽  
Author(s):  
S. Veenbergen ◽  
P. Li ◽  
H. C. Raatgeep ◽  
D. J. Lindenbergh-Kortleve ◽  
Y. Simons-Oosterhuis ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cells ◽  
Dendritic Cells ◽  
Bowel Disease ◽  
Cd4 T Cells ◽  
Inflammatory Bowel

scholarly journals Carboxylesterase-1 assisted targeting of HDAC inhibitors to mononuclear myeloid cells in Inflammatory Bowel Disease

2021 ◽  
Author(s):  
Ahmed M I Elfiky ◽  
Mohammed Ghiboub ◽  
Andrew Y F Li Yim ◽  
Ishtu L Hageman ◽  
Jan Verhoeff ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
T Cell ◽  
Human Blood ◽  
Bowel Disease ◽  
Cell Transfer ◽  
Inflammatory Bowel ◽  
Carboxylesterase 1 ◽  
T Cell Transfer

Abstract Background and Aims Histone deacetylase inhibitors (HDACi) exert potent anti-inflammatory effects. Because of the ubiquitous expression of HDACs, clinical utility of HDACi is limited by off-target effects. Esterase-sensitive motif (ESM) technology aims to deliver ESM-conjugated compounds to human mononuclear myeloid cells, based on their expression of carboxylesterase 1 (CES1). This study aims to investigate utility of an ESM-tagged HDACi in inflammatory bowel disease (IBD). Methods CES1 expression was assessed in human blood, in vitro differentiated macrophage and dendritic cells and Crohn's disease (CD) colon mucosa by mass cytometry, quantitative PCR and immunofluorescence staining respectively. ESM-HDAC528 intracellular retention was evaluated by mass spectrometry. Clinical efficacy of ESM-HDAC528 was tested in DSS-induced colitis and T cell transfer colitis models using transgenic mice expressing human CES1 under the CD68 promotor. Results CES1 mRNA was highly expressed in human blood CD14 + monocytes, in vitro differentiated and LPS stimulated macrophages and dendritic cells. Specific hydrolysis and intracellular retention of ESM-HDAC528 in CES1 + cells was demonstrated. ESM-HDAC528 inhibited LPS-stimulated IL-6 and TNF-α production 1000 times more potently than its control, HDAC800, in CES1 high monocytes. In healthy donors peripheral blood, CES1 expression was significantly higher in CD14 ++CD16 - monocytes compared to CD14 +CD16 ++ monocytes. In CD inflamed colon, a higher number of mucosal CD68 + macrophages expressed CES1 compared to non-inflamed mucosa. In vivo, ESM-HDAC528 reduced monocyte differentiation in the colon and significantly improved colitis in a T cell transfer model, whilst having limited potential in ameliorating DSS-induced colitis. Conclusions We demonstrate that monocytes and inflammatory macrophages specifically express CES1, and can be preferentially targeted by ESM-HDAC528 to achieve therapeutic benefit in IBD.

scholarly journals Dendritic cell profiles in the inflamed colonic mucosa predict the responses to tumor necrosis factor alpha inhibitors in inflammatory bowel disease

2018 ◽  
Vol 52 (4) ◽  
pp. 443-452
Author(s):  
Natasa Smrekar ◽  
David Drobne ◽  
Lojze M. Smid ◽  
Ivan Ferkolj ◽  
Borut Stabuc ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
Dendritic Cell ◽  
Tumor Necrosis Factor ◽  
Bowel Disease ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Inflammatory Bowel ◽  
Factor Alpha ◽  
Necrosis Factor

Abstract Background Dendritic cells play crucial roles in the control of inflammation and immune tolerance in the gut. We aimed to investigate the effects of tumor necrosis factor alpha (TNFa) inhibitors on intestinal dendritic cells in patients with inflammatory bowel disease and the potential role of intestinal dendritic cells in predicting the response to treatment. Patients and methods Intestinal biopsies were obtained from 30 patients with inflammatory bowel disease before and after treatment with TNFa inhibitors. The proportions of lamina propria dendritic cell phenotypes were analysed using flow cytometry. Disease activity was endoscopically assessed at baseline and after the induction treatment. Results At baseline, the proportion of conventional dendritic cells was higher in the inflamed mucosa (7.8%) compared to the uninflamed mucosa (4.5%) (p = 0.003), and the proportion of CD103+ dendritic cells was lower in the inflamed mucosa (47.1%) versus the uninflamed mucosa (57.3%) (p = 0.03). After 12 weeks of treatment, the proportion of conventional dendritic cells in the inflamed mucosa decreased from 7.8% to 4.5% (p = 0.014), whereas the proportion of CD103+ dendritic cells remained unchanged. Eighteen out of 30 (60%) patients responded to their treatment by week 12. Responders had a significantly higher proportion of conventional dendritic cells (9.16% vs 4.4%, p < 0.01) with higher expression of HLA-DR (median fluorescent intensity [MFI] 12152 vs 8837, p = 0.038) in the inflamed mucosa before treatment compared to nonresponders. Conclusions A proportion of conventional dendritic cells above 7% in the inflamed inflammatory bowel disease mucosa before treatment predicts an endoscopic response to TNFa inhibitors.

Microbiota Small RNAs in Inflammatory Bowel Disease

2016 ◽  
Vol 25 (4) ◽  
pp. 509-516 ◽  
Author(s):  
Anca T. Filip ◽  
Ovidiu Balacescu ◽  
Catalin Marian ◽  
Andrei Anghel
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
Rna Interference ◽  
Mirna Expression ◽  
Bowel Disease ◽  
B Cell Lymphoma ◽  
Lactobacillus Delbrueckii ◽  
Host Cells ◽  
E Coli ◽  
Inflammatory Bowel

MiRNAs are a class of potential gene regulators of critical importance in Inflammatory Bowel Disease (IBD). This review aims to present the connection between gut microbiota, probiotics administration and microRNA (miRNA) expression in IBD. It also brings into question cross-kingdom RNAi (RNA interference). Not only that gut host cells garden the intestinal microbiome via miRNA, but also strong evidence supports the idea that different species of bacteria have an impact on the intestinal immune response by modulating miRNA expression. Cross-kingdom RNAi refers to RNA silencing signals that travel between two unrelated, interacting organisms. RNAs communication between prokaryotes and eukaryotes (bacteria and nematodes) via RNAs transfer has been proved. Some authors also support the idea that non-coding RNAs are being transferred by bacterial pathogens to the host cells as part of the intracellular infection process. Further studies are required in order to clarify whether the mechanism by which bacteria modulate miRNA expression concerns RNAs transfer. These findings may lead to a different approach to IBD therapy in the future. Abbreviations: AChE: Acetylcholinesterase; AIEC: Adherent-invasive E coli; ATF: Activating transcription factor; Bcl-2: B-cell lymphoma 2; BMDC: Bone marrow-derived dendritic cells; C elegans: Caenorhabditis elegans; CCL: Chemokine C-C motif ligand; CD: Crohn’s disease; CDC42: Cell division control protein 42 homolog; CXCL: Chemokine (C-X-C motif) ligand; DC: Dendritic cells; E Coli: Escherichia coli; EcN: E coli Nissle; EPEC: Entheropathogenic E coli; FOXO3: Forkhead box protein O3; GF: Germ-free; IBD: Inflammatory bowel disease; IECs: Intestinal epithelial cells; IGLC: Immunoglobulin Lambda Constant Region; IkB: Inhibitor of NF-Kb; IL: Interleukin; IRGM: Immunity-related GTPase family M protein; L del: Lactobacillus delbrueckii; LGG: Lactobacillus rhamnosus GG; MAPK: Mitogen-activated protein kinases; miRNA: MicroRNA; mRNA: Messenger RNA; MyD88: Myeloid differentiation primary response gene 88; NF-kB: Nuclear factor kappa B; NOD2: Nucleotide-binding oligomerization domain-containing protein 2; PAR: Partitioning defective protein; RhoB: Ras Homolog Family Member B; RISC: RNA induced silencing complex; RNAi: RNA interference; SHH: Sonic hedgehog (gene); SPF: Specific-pathogen-free; SRNA: Small RNA; STAT3: Signal transducer and activator of transcription 3; TGF: Transforming growth factor; Th17: T helper 17 cells; TJ: Tight junction; TLR: Toll like receptor; TNF: Tumor necrosis factor; UC: Ulcerative colitis; Xcv: Xanthomonas campestris pv. Vesicatoria; ZO-2: Zonula occludens-2.

scholarly journals Immunomodulatory Effect of Gut Microbiota-Derived Bioactive Peptides on Human Immune System from Healthy Controls and Patients with Inflammatory Bowel Disease

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2605 ◽  
Author(s):  
Samuel Fernández-Tomé ◽  
Alicia C. Marin ◽  
Lorena Ortega Moreno ◽  
Montserrat Baldan-Martin ◽  
Irene Mora-Gutiérrez ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
B Cells ◽  
Bowel Disease ◽  
Bioactive Peptides ◽  
Bifidobacterium Longum ◽  
Healthy Controls ◽  
Human Immune System ◽  
Cytokine Milieu ◽  
Inflammatory Bowel

Bioactive peptides secreted by probiotic Bifidobacterium longum (peptide B7) and opportunistic pathogen Bacteroides fragilis (peptide B12) modulate the intestinal cytokine milieu in health. Here, we characterized their capacity to modulate both the mucosal cytokine production and the phenotype of circulating antigen presenting cells (APCs) in active inflammatory bowel disease (IBD). The IBD mucosa produced higher levels of pro-inflammatory cytokines referred to healthy controls (HCs). Peptides B7 and B12, however, did not ameliorate the mucosal cytokine milieu in IBD. Human circulating APCs (B-cells, monocytes, plasmacytoid dendritic cells (pDCs), and conventional dendritic cells (cDCs)) were characterized by flow cytometry in presence/absence of the peptides. Circulating B-cells, monocytes, and cDCs from IBD patients were more activated than those from HCs. Peptide B7, but not B12, decreased CCR2 expression on all APC subsets from HC, but not IBD patients. Moreover, both peptides tend to further increase their pro-inflammatory profile in IBD. In summary, IBD patients display mucosal and circulating APC pro-inflammatory properties. Peptide B7 immunomodulatory capacity elicited over circulating APCs from HC, but not IBD patients, suggests the presence of disrupted modulatory mechanisms for this peptide in IBD. Future studies should address the effect of bacteria-derived immunomodulatory peptides in non-inflamed (quiescent) IBD patients.

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