Regulation of CEACAM Family Members by IBD-Associated Triggers in Intestinal Epithelial Cells, Their Correlation to Inflammation and Relevance to IBD Pathogenesis

Saiz-Gonzalo, Gonzalo; Hanrahan, Naomi; Rossini, Valerio; Singh, Raminder; Ahern, Mary; Kelleher, Maebh; Hill, S.; O'Sullivan, Ruairi; Fanning, Áine; Walsh, Patrick; Hussey, Séamus; Shanahan, Fergus; Nally, Ken; O’Driscoll, Caitriona M.; Melgar, Silvia

doi:10.3389/fimmu.2021.655960

Cited by 26 publications

(18 citation statements)

References 41 publications

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“…Both molecules were recognized to be highly present in human colon epithelia and related to inflammation and tumorigenesis [41]. Defects in CEACAM signalling in intestinal epithelial cells are associated with Inflammatory Bowel Disease (IBD), and even Colitis-Associated Cancer (CAC) [41, 42]. As we revealed the interplay of various cell types including colonocytes and cycling cells in CEACAM1 CEACAM5 interaction in IBD or colorectal cancer patients, it might highlight targeting these cells to reverse the adverse conditions.…”

Section: Resultsmentioning

confidence: 99%

SpatialDM: Rapid identification of spatially co-expressed ligand-receptor reveals cell-cell communication patterns

Wang

Liu

et al. 2022

Preprint

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Cell-cell communication is a key aspect of dissecting the complex cellular microenvironment. Existing single-cell and spatial transcriptomics-based methods primarily focus on identifying cell-type pairs having a specific interaction, while less attention has been paid to the prioritisation of interaction features. Here, we introduce SpatialDM, a statistical model and toolbox leveraging a bivariant Moran's statistic to detect spatially co-expressed ligand and receptor, their local interacting spots, and communication patterns. By deriving an analytical null distribution, this method is scalable to millions of spots and shows accurate and robust performance in various simulations. On one melanoma and multiple intestinal datasets, SpatialDM reveals promising communication patterns and identifies differential interactions between conditions, hence enabling the discovery of context-specific cell cooperation and signalling.

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Section: Resultsmentioning

confidence: 99%

SpatialDM: Rapid identification of spatially co-expressed ligand-receptor reveals cell-cell communication patterns

Wang

Liu

et al. 2022

Preprint

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“…Dead cells were excluded using LIVE/DEAD™ Fixable Dead Cell Stain Kits. Anti–CEACAM1–specific mouse monoclonal antibody (clone number 283340) was shown to be non-cross-reactive with other CEACAM families as described previously ( 15 ). Flow cytometry was performed on a FACS–Canto II (BD Biosciences, Franklin Lakes, NJ, USA) and data were analyzed using FlowJo software (BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

Increased CEACAM1 expression on peripheral blood neutrophils in patients with rheumatoid arthritis

Matsumoto

Fujita²,

Onizawa³

et al. 2022

Front. Immunol.

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Altered expression of adhesion molecules in immune cells has been demonstrated in rheumatoid arthritis (RA). Carcinoembryonic–antigen–related cell–adhesion molecule 1 (CEACAM1) is an adhesion molecule that acts as a coinhibitory receptor in the immune system. We investigated the role of CEACAM1 in immune cell subsets of patients with RA. Peripheral blood was obtained from 37 patients with RA and 20 healthy controls (HC). The expression of CEACAM1 and T–cell immunoglobulin mucin domain molecule (TIM) –3 on peripheral blood mononuclear cells and neutrophils was analyzed by flow cytometry. Intracellular TIM–3 expression was analyzed using cellular lysates by Western blot analysis. Serum levels of soluble CEACAM1 (sCEACAM1) were estimated by an enzyme-linked immunosorbent assay. CEACAM1 expression was not detected in peripheral blood mononuclear cells, including in CD14(+) monocytes and CD3(+) lymphocytes isolated from patients with RA or HC. However, substantial cell–surface expression of CEACAM1 was detected in peripheral blood neutrophils, and it was significantly elevated in samples from patients with RA without remission compared to those in remission. There was no significant difference in serum levels of sCEACAM1 between patients with RA and HC. Cell-surface expression of TIM-3 was not detected in peripheral blood neutrophils from patients with RA or HC but was seen in CD14(+) monocytes. However, there was no significant difference in TIM–3 expression on monocytes between patients with RA and HC. Our data indicate that cell-surface expression of CEACAM1 on peripheral blood neutrophils are higher in patients with RA and that it is associated with rheumatoid inflammation. Further studies are needed to explore the potential role of CEACAM1 in rheumatoid inflammatory pathways.

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“…Western blot was performed as described with some modifications (Saiz-Gonzalo et al, 2021). Briefly, colonic tissue samples were homogenised in tissue lysis buffer (50 mM NaCl, 50 mM NaF, 50 mM Na 4 P 2 O 7 , 5 mM EGTA, 5 mM EDTA, 2 mM Na3VO4, 10 mM HEPES, 1% Triton X-100, pH 7.4) supplemented with 1 × Halt Protease and Phosphatase Inhibitor Cocktail (cat no.…”

Section: Methodsmentioning

confidence: 99%

An IBD-associated pathobiont synergises with NSAID to promote colitis which is blocked by NLRP3 inflammasome and Caspase-8 inhibitors

Singh

Rossini

Stockdale

et al. 2022

Preprint

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Conflicting evidence exists on the association between consumption of non-steroidal anti-inflammatory drugs (NSAIDs) and symptomatic worsening of inflammatory bowel disease (IBD). We hypothesise that the heterogeneous prevalence of pathobionts [e.g., adherent-invasive Escherichia coli (AIEC)], might explain this inconsistent NSAIDs/IBD correlation. Using IL10-/- mice, we show aggravation of colitis in AIEC-colonised animals fed NSAID. This is accompanied by activation of the NLRP3 inflammasome, Caspase-8, apoptosis and pyroptosis; features not seen in mice exposed to AIEC or NSAID alone, revealing an AIEC/NSAID synergistic effect. Inhibition of NLRP3 or Caspase-8 activity ameliorated colitis, with reduction in NLRP3 inflammasome activation, cell death markers and activated T-cells and macrophages, improved histology and increased abundance of Clostridium cluster XIVa species. Our findings provide mechanistic insights into how NSAID and an opportunistic gut-pathobiont can synergise to worsen IBD symptoms. Thus, targeting the NLRP3 inflammasome and Caspase-8 could be a potential therapeutic strategy in patients with NSAID-worsened inflammation.

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Regulation of CEACAM Family Members by IBD-Associated Triggers in Intestinal Epithelial Cells, Their Correlation to Inflammation and Relevance to IBD Pathogenesis

Cited by 26 publications

References 41 publications

SpatialDM: Rapid identification of spatially co-expressed ligand-receptor reveals cell-cell communication patterns

SpatialDM: Rapid identification of spatially co-expressed ligand-receptor reveals cell-cell communication patterns

Increased CEACAM1 expression on peripheral blood neutrophils in patients with rheumatoid arthritis

An IBD-associated pathobiont synergises with NSAID to promote colitis which is blocked by NLRP3 inflammasome and Caspase-8 inhibitors

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