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  1. Article: Triggering receptor expressed on myeloid cells-1 deletion in mice attenuates high-fat diet-induced obesity.

    Brustolin, Benjamin / Touly, Nina / Maillefer, Marine / Parisot, Lola / Di Pillo, Elisa / Derive, Marc / Gibot, Sébastien

    Frontiers in endocrinology

    2023  Volume 13, Page(s) 983827

    Abstract: Introduction: The low-grade inflammatory state present in obesity leads to the development and perpetuation of comorbidities associated with obesity. Our laboratory has been working for several years on an amplification loop of the inflammatory response ...

    Abstract Introduction: The low-grade inflammatory state present in obesity leads to the development and perpetuation of comorbidities associated with obesity. Our laboratory has been working for several years on an amplification loop of the inflammatory response mediated by TREM-1 (Triggering Receptor of Expressed on Myeloid Cells-1). It is implicated in many acute (septic shock) and chronic (IBD) inflammatory diseases. Previously, TREM-1 has been shown to be overexpressed in adipose and liver tissue in obese and diabetic patients, but its impact has never been characterized in these pathologies.
    Methods: Our hypothesis is that TREM-1 plays a major role in the generation and perpetuation of inflammation during obesity and its associated complication (Insulin resistance and cardiac dysfunction). We assessed TREM-1 protein expression by western blot and immunofluorescence in omental and subcutaneous (pre-)adipocyte. Moreover, we submitted mice to a high-fat diet and investigated the effects of the genetic
    Results: We showed, for the first time, that TREM-1 is expressed and is functional in subcutaneous and omental (pre-)adipocytes. In the mouse model of high-fat diet-induced obesity, we found that
    Discussion/conclusion: Our results reveal the
    MeSH term(s) Animals ; Mice ; Diet, High-Fat/adverse effects ; Inflammation/metabolism ; Insulin Resistance/genetics ; Myeloid Cells ; Obesity/genetics ; Obesity/metabolism ; Triggering Receptor Expressed on Myeloid Cells-1/genetics
    Chemical Substances Triggering Receptor Expressed on Myeloid Cells-1 ; TREM1 protein, mouse
    Language English
    Publishing date 2023-01-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2022.983827
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Soluble TREM-1 plasma concentration predicts poor outcome in COVID-19 patients.

    Gibot, Sébastien / Lafon, Thomas / Jacquin, Laurent / Lefevre, Benjamin / Kimmoun, Antoine / Guillaumot, Anne / Losser, Marie-Reine / Douplat, Marion / Argaud, Laurent / De Ciancio, Guillaume / Jolly, Lucie / Touly, Nina / Derive, Marc / Malaplate, Catherine / Luc, Amandine / Baumann, Cédric / François, Bruno

    Intensive care medicine experimental

    2023  Volume 11, Issue 1, Page(s) 51

    Abstract: Background: The immuno-receptor Triggering Expressed on Myeloid cells-1 (TREM-1) is activated during bacterial infectious diseases, where it amplifies the inflammatory response. Small studies suggest that TREM-1 could be involved in viral infections, ... ...

    Abstract Background: The immuno-receptor Triggering Expressed on Myeloid cells-1 (TREM-1) is activated during bacterial infectious diseases, where it amplifies the inflammatory response. Small studies suggest that TREM-1 could be involved in viral infections, including COVID-19. We here aim to decipher whether plasma concentration of the soluble form of TREM-1 (sTREM-1) could predict the outcome of hospitalized COVID-19 patients.
    Methods: We conducted a multicentre prospective observational study in 3 university hospitals in France. Consecutive hospitalized patients with confirmed infection with SARS-CoV-2 were enrolled. Plasma concentration of sTREM-1 was measured on admission and then at days 4, 6, 8, 14, 21, and 28 in patients admitted into an ICU (ICU cohort: ICUC) or 3 times a week for patients hospitalized in a medical ward (Conventional Cohort: ConvC). Clinical and biological data were prospectively recorded and patients were followed-up for 90 days. For medical ward patients, the outcome was deemed complicated in case of requirement of increased oxygen supply > 5 L/min, transfer to an ICU, or death. For Intensive Care Unit (ICU) patients, complicated outcome was defined by death in the ICU.
    Results: Plasma concentration of sTREM-1 at inclusion was higher in ICU patients (n = 269) than in medical ward patients (n = 562) (224 pg/mL (IQR 144-320) vs 147 pg/mL (76-249), p < 0.0001), and higher in patients with a complicated outcome in both cohorts: 178 (94-300) vs 135 pg/mL (70-220), p < 0.0001 in the ward patients, and 342 (288-532) vs 206 pg/mL (134-291), p < 0.0001 in the ICU patients. Elevated sTREM-1 baseline concentration was an independent predictor of complicated outcomes (Hazard Ratio (HR) = 1.5 (1.1-2.1), p = 0.02 in ward patients; HR = 3.8 (1.8-8.0), p = 0.0003 in ICU patients). An sTREM-1 plasma concentration of 224 pg/mL had a sensitivity of 42%, and a specificity of 76% in the ConvC for complicated outcome. In the ICUC, a 287 pg/mL cutoff had a sensitivity of 78%, and a specificity of 74% for death. The sTREM-1 concentrations increased over time in the ConvC patients with a complicated outcome (p = 0.017), but not in the ICUC patients.
    Conclusions: In COVID-19 patients, plasma concentration of sTREM-1 is an independent predictor of the outcome, although its positive and negative likelihood ratio are not good enough to guide clinical decision as a standalone marker.
    Language English
    Publishing date 2023-08-14
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2740385-3
    ISSN 2197-425X
    ISSN 2197-425X
    DOI 10.1186/s40635-023-00532-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The role of platelets and von Willebrand factor in the procoagulant phenotype of inflammatory bowel disease.

    Schellenberg, Célia / Lagrange, Jérémy / Ahmed, Muhammad Usman / Arnone, Djésia / Campoli, Philippe / Louis, Huguette / Touly, Nina / Caron, Bénédicte / Plénat, François / Perrin, Julien / Lenting, Peter J / Regnault, Véronique / Lacolley, Patrick / Denis, Cécile V / Peyrin-Biroulet, Laurent

    Journal of Crohn's & colitis

    2023  

    Abstract: Objective: Although the risk for thrombosis is well documented for inflammatory bowel disease (IBD) patients, the underlying pathological mechanism seems to be different from other thrombotic conditions. Deciphering the actors responsible for the ... ...

    Abstract Objective: Although the risk for thrombosis is well documented for inflammatory bowel disease (IBD) patients, the underlying pathological mechanism seems to be different from other thrombotic conditions. Deciphering the actors responsible for the increased risk of thrombosis in IBD would help to improve management of this frequent complication.
    Design: We studied the interplay between platelets, coagulation, and von Willebrand factor (VWF) in 193 IBD patients and in experimental models (acute and chronic) of colitis in wild-type and VWF-deficient mice.
    Results: We found a platelet-dependent increase in thrombin generation in IBD patients and in our mouse model of colitis. Agglutinated platelets were present in the blood of patients and mice. Interestingly, we observed not only a significant increase in total VWF antigen, but we were able to detect the presence of active VWF (VWF in its platelet-binding conformation; 3.2±2.7µg/ml) in the plasma of 30% of all IBD patients. In healthy controls, active VWF levels were below 0.3µg/ml. This led us to further explore experimental colitis in VWF-deficient mice and we observed that these mice were protected against the procoagulant state triggered by the colitis. Unexpectedly, these mice also manifested a significant worsening of colitis severity both in acute and chronic models.
    Conclusion: Platelets and VWF (including its active form) appear to be central players in the procoagulant phenotype in IBD. We observed that the role of VWF in hemostasis differs from its role in colic tissue healing, potentially opening new therapeutic avenues for a life-threatening complication in IBD patients.
    Language English
    Publishing date 2023-11-27
    Publishing country England
    Document type Journal Article
    ZDB-ID 2390120-2
    ISSN 1876-4479 ; 1873-9946
    ISSN (online) 1876-4479
    ISSN 1873-9946
    DOI 10.1093/ecco-jcc/jjad198
    Database MEDical Literature Analysis and Retrieval System OnLINE

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