Biology subjects

Dejardin, F.

Publications and source records attributed to Dejardin, F..

4 recordsLinked to original sources

bioRxiv2026

ILC3s are Required for Enterocyte Homeostasis to Food Intake

Food provides nutrients that are selectively absorbed by the intestine, but, at the same time, may contain elements that challenge the intestinal barrier and induce post-prandial inflammation (PPI). How PPI is controlled in order to avoid pathological perturbation of homeostasis remains unclear. Here, we report that during fasting, enterocytes increase their absorptive potential and oxidative metabolism, a program that is largely reversed upon food intake of lipids that perturb the intestinal barrier and induce PPI. Such perturbation is countered by ILC3s, in the absence of which PPI increases, program reversal does not occur, and enterocytes engage into excessive oxidative metabolism. This enterocyte state leads to critical hypoglycemia as a consequence of decreased glucose absorption and increased insulinemia, recapitulating the pathological situation found in patients suffering from intestinal damage and sepsis. We hereby uncover a critical function for ILC3s in maintaining enterocyte homeostasis upon challenging food intake.

immunology↗

bioRxiv2024

Imperfect hairpins formed by CTG trinucleotide repeats are heteroduplex DNA molecules in living cells

There are over fifty microsatellite expansion disorders, often neurodegenerative pathologies, due to large expansions of tandem repeat sequences. These microsatellites vary in motif composition, size and copy number in the genome. The ability of these repeats to form secondary structures in vitro is strongly suspected to trigger the expansion process and therefore, the pathology. However, there is no formal proof that similar structures are formed in vivo, in living and replicating cells. We are focused on the CTG trinucleotide repeat whose expansion is responsible for myotonic dystrophy type 1 (DM1 or Steinert disease), affecting 1 in 8,000 people worldwide. A series of llama nanobodies (VHH) were selected to bind to the secondary structure formed by a synthetic imperfect CTG hairpin. Yeast one-hybrid was used to identify VHH that were able to activate a reporter gene in vivo . One of them was shown to be very specific since it binds a CTG hairpin but not a CAG hairpin or a GC-rich sequence. This nanobody also bind to long CTG trinucleotide repeats carried by plasmidic or genomic DNAs, proportionally to the number of repeats, suggesting that longer repeats tend to form more frequently imperfect hairpins. Finally, the VHH was bound to a protein G column and used to selectively enrich structure-containing DNA molecules, that were further observed by electron microscopy. They exhibit different kinds of structures in which only one strand is folded into an imperfect hairpin. Our results unambiguously show that alternative DNA structures are transiently formed by CTG trinucleotide repeats in living bacterial and yeast cells and suggest that imperfect CTG hairpins mainly exist in vivo mainly as heteroduplex DNA molecules.

molecular biology↗

bioRxiv2023

A monoclonal antibody collection for C. difficile typing

Clostridioides difficile is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis in adults. Various C. difficile strains circulate currently, associated with different outcomes and antibiotic resistance profiles. However, most studies still focus on the reference strain 630 that does not circulate anymore, partly due to the lack of immunological tools to study current clinically important C. difficile PCR ribotypes. Herein, we immunized mice expressing human variable antibody genes with the Low Molecular Weight (LMW) subunit of the surface layer protein SlpA from various C. difficile strains. Monoclonal antibodies purified from hybridomas bound LMW with high-affinity and whole bacteria from current C. difficile ribotypes with different cross-specificities. This first collection of anti-C. difficile mAbs represent valuable tools for basic and clinical research.

immunology↗

bioRxiv2019

Innate immune recognition of a bacterial MAMP leads to conditional activation of pro- or anti-inflammatory responses

Microbe-associated molecular patterns (MAMPs) are recognized by pattern recognition receptors (PRRs) of the innate immune system. Flagellin, the primary component of bacterial flagella, is recognized by membrane TLR5 and cytoplasmic NLRC4 receptors, which promote a vigorous pro-inflammatory response typically associated with bacterial infection. However, herein, we report that the nature of the flagellin-induced response is highly dependent on the physiological state of the tissue. Specifically, in the steady state, epithelial cell detection of flagellin orchestrates an anti-inflammatory response mediated by IL-33-dependent type 2 regulatory T cells while, in the context of injury, it induces a pro-inflammatory response mediated by myeloid cells, IL-18 and Th17 cells. Likewise, in the absence of infection, bacterial symbionts expressing high levels of flagellin induce a type 2 response. These data demonstrate that, depending on the inflammatory state of the milieu, MAMPs can function both as immunogens or tolerogens.

immunology↗