Nature Portfolio’s Post

Transglutaminase 2 (TG2) plays a pivotal role in the pathogenesis of celiac disease (CeD) by deamidating dietary gluten peptides, which facilitates antigenic presentation and a strong anti-gluten T cell response. Here, we elucidate the molecular mechanisms underlying the efficacy of the TG2 inhibitor ZED1227 by performing transcriptional analysis of duodenal biopsies from individuals with CeD on a long-term gluten-free diet before and after a 6-week gluten challenge combined with 100 mg per day ZED1227 or placebo. At the transcriptome level, orally administered ZED1227 effectively prevented gluten-induced intestinal damage and inflammation, providing molecular-level evidence that TG2 inhibition is an effective strategy for treating CeD. ZED1227 treatment preserved transcriptome signatures associated with mucosal morphology, inflammation, cell differentiation and nutrient absorption to the level of the gluten-free diet group. Nearly half of the gluten-induced gene expression changes in CeD were associated with the epithelial interferon-γ response. Moreover, data suggest that deamidated gluten-induced adaptive immunity is a sufficient step to set the stage for CeD pathogenesis. Our results, with the limited sample size, also suggest that individuals with CeD might benefit from an HLA-DQ2/HLA-DQ8 stratification based on gene doses to maximally eliminate the interferon-γ-induced mucosal damage triggered by gluten.

Hypothesis: "Some individuals with PASC may not fully clear the coronavirus SARS-CoV-2 after acute infection." Here they review studies that have identified SARS-CoV-2 RNA/protein or immune responses indicative of a SARS-CoV-2 reservoir in PASC samples. "The aim was to identify research priorities to guide the further study of a SARS-CoV-2 reservoir in PASC, with the goal that clinical trials of antivirals or other therapeutics with potential to clear a SARS-CoV-2 reservoir are accelerated." #PASC #longcovid #viralreservoir https://lnkd.in/e9JwKpf8

We have just celebrated an International Day of Immunology under the theme: Immunity Through the Ages: Navigating the Science of Aging and Immunology. Here at Institute of Pharmaceutical Sciences of Western Switzerland (ISPSO)- University of Geneva multiple groups work on various topics from vaccines to understanding diseases and fight against infection, autoimmunity, and cancer. #ImmunologyDay #ImmunityThroughTheAges #CelebrateImmuneSystem

#immunology #inflammation #treatment #medicine https://lnkd.in/gUhATM3z Given the strong pro-inflammatory role of IL-17, agents that target IL-17 or the IL-17 receptor (IL-17R) are attractive candidates for inflammatory diseases. Examples are the IL-17 inhibitor #secukinumab and the IL-17R inhibitor brodalumab, which are both approved for the treatment of #psoriasis. However, these agents have unexpectedly low efficacy in IL-17-related diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS). Investigating the underlying mechanisms, Luo et al. discovered that IL-17 can, over time, induce excessive expression of the tyrosine phosphatase SHP2. SHP2 binds to the TRAF domain of the IL-17R-associated adaptor protein ACT1, displacing the ACT1-interaction partner TRAF5 and inducing ACT1 dephosphorylation. The resulting ACT1–SHP2 complex mediates the autonomous activation of IL-17R signalling, thereby sustaining inflammation and facilitating resistance to IL-17-directed therapy. Tissues from patients with IL-17-related autoimmune diseases, and related tissues from respective animal models, reveal overexpression of SHP2. The authors find that SHP2 inhibitors, as well as iguratimod, a small molecule drug that disrupts the ACT1–SHP2 interaction, show promise in mouse models of MS and RA.

Congratulations to Regeneron! Veopoz, a fully human monoclonal antibody, has received FDA approval for treating patients with CHAPLE disease. 🏥 CHAPLE disease, also known as CD55-deficient protein-losing enteropathy, is an extremely rare but life-threatening hereditary immune disease caused by an overactivation of the complement system due to mutations in the CD55 gene. The complement system is part of our immune system which helps to destroy microbes. There are an estimated less than 100 patients with CHAPLE disease worldwide. Veopoz (pozelimab-bbfg) is an IgG4 antibody which blocks the activity of complement factor C5, a protein involved in complement system activation. It binds with high affinity to both wild-type and variant human C5. Currently, Veopoz is being investigated as a combination therapy with cemdisiran to treat other complement-mediated disorders. Read the press release here: https://lnkd.in/etUK_EQW #Biointron #FDA #Immunotherapy #Antibodies #PharmaNews #DrugDevelopment #CHAPLE Image from NIAID

CD4+ and CD8+ T lymphocytes are white blood cells that protect the body from pathogens, but they can also become active against healthy cells leading to disease. In our last publication, we developed a fully human 3D model system to study the interaction between T cells and intestinal epithelial cells using intestinal organoids. We show that chemotherapy-damaged intestinal epithelial cells release galectin-9 upon damage, promoting T cell migration and activation that can further compromise epithelial homeostasis. This may provide novel strategies for prevention or therapeutic intervention in pathologies like graft-versus-host disease. Check it out! Thanks to Suze Jansen, Paul Coffer, Caroline Lindemans and all co-authors for making this work possible. #lymphocytes #Tcells #organoids #intestinalepithelium #exvivo #chemotherapy #galectin9 #Gal9 #GVHD #immunology

Teva Pharmaceutical Industries is teaming up with Sanofi to develop a potential blockbuster drug for inflammatory bowel disease. Sanofi will invest $1.5 billion in Teva's anti-TL1A drug, currently in phase 2 trials, with phase 3 trials expected in 2025. The drug targets Crohn's disease and ulcerative colitis, aiming for a commercial launch around 2028. Both companies will share development costs and potential profits globally, with Sanofi leading phase 3 trials, and Teva handling commercialization in Europe and other specified regions. This collaboration signifies the potential of the anti-TL1A drug in addressing serious gastrointestinal diseases. #Pharmaceuticals #InflammatoryBowelDisease #MedicalResearch #Collaboration #DrugDevelopment #Sanofi #TevaPharmaceuticals #TL1A #CrohnsDisease #UlcerativeColitis #HealthcareInnovation

#BreakingNews: Biosimilars Revolutionizing Immunology! Check out the hottest updates from the Biosimilars Immunology Roundup! #Biosimilars2023 #ImmunologyAdvancements

RNA interference with Fazirsiran reduces globule burden in alpha-1-antitrypsin deficiency liver disease. A phase 2 placebo controlled trial (SEQUOIA) Within a multinational phase 2 study with Fazirsiran, an RNA interference drug, in alpha-1-antitrypsin (AAT) deficiency liver disease we were able to show efficacy (94% reduction in Z-AAT and reduced globule burden and reduced hepatic inflammation), without severe side effects and without change in lung function. Details of the study can now be read in Gastroenterology.

Thanks to the very effective contribution from all of the authors : a recent published study on Molecular docking as a tool for the discovery of novel insight about the role of acid sphingomyelinase inhibitors in SARS- CoV-2 infectivity. _ In this review, we identified the metabolism of sphingolipids, sphingolipids' role in cell signal transduction cascades, and viral infection mechanisms. Also, we outlined ASMase structure and underlying mechanisms inhibiting viral entry 40 with the aid of inhibitors of acid sphingomyelinase (FIASMAs). In silico molecular docking analyses of FIASMAs with inhibitors revealed that dilazep (S = − 12.58 kcal/mol), emetine (S = − 11.65 kcal/mol), pimozide (S = − 11.29 kcal/mol), carvedilol (S = − 11.28 kcal/mol), mebeverine (S = − 11.14 kcal/mol), cepharanthine (S = − 11.06 kcal/mol), hydroxyzin (S = − 10.96 kcal/mol), astemizole (S = − 10.81 kcal/mol), sertindole (S = − 10.55 kcal/mol), and bepridil (S = − 10.47 kcal/mol) have higher inhibition activity than the candidate drug amiodarone (S = − 10.43 kcal/mol), making them better options for inhibition. ORCID : https://lnkd.in/gjCZttmg https://lnkd.in/gtVaaEDj