Impact of Antigen Presentation Mechanisms on Immune Response in Autoimmune Hepatitis

The liver is a very tolerogenic organ. It is continually exposed to a multitude of antigens and is able to promote an effective immune response against pathogens and simultaneously immune tolerance against self-antigens. In spite of strong peripheral and central tolerogenic mechanisms, loss of tolerance can occur in autoimmune liver diseases, such as autoimmune hepatitis (AIH) through a combination of genetic predisposition, environmental factors, and an imbalance in immunological regulatory mechanisms. The liver hosts several types of conventional resident antigen presenting cells (APCs) such as dendritic cells, B cells and macrophages (Kupffer cells), and unconventional APCs including liver sinusoidal endothelial cells, hepatic stellate cells and hepatocytes. By standard (direct presentation and cross-presentation) and alternative mechanisms (cross-dressing and MHC class II-dressing), liver APCs presents self-antigen to naive T cells in the presence of costimulation leading to an altered immune response that results in liver injury and inflammation. Additionally, the transport of antigens and antigen:MHC complexes by trogocytosis and extracellular vesicles between different cells in the liver contributes to enhance antigen presentation and amplify autoimmune response. Here, we focus on the impact of antigen presentation on the immune response in the liver and on the functional role of the immune cells in the induction of liver inflammation. A better understanding of these key pathogenic aspects could facilitate the establishment of novel therapeutic strategies in AIH

Modes d’habiter à Pompéi à l’époque républicaine : diffusion et utilisation du type de la maison à atrium testudinatum

Données scientifiques produites : https://centrejeanberard.cnrs.fr/spip.php?article400&lang=fr Chroniques de l’EFR :http://journals.openedition.org/cefr/4796 Introduction Le projet, initié sur le terrain en juillet 2019, est centré sur l’habitat urbain de Pompéi, en particulier sur les maisons à atrium testudinatum, et fait l’objet d’une double approche, architecturale et sociologique. Le projet, porté par l’université Paris Nanterre, est inscrit dans les programmes du Centre Jean Bérard (U..

Arpi

Dans le cadre du programme « Arpi. Formes et vie d’une cité italiote » qui a débuté en 2014, le Centre Jean Bérard (USR 3133 CNRS-EFR) et l’Université de Salerne, en collaboration avec la Surintendance archéologique des Pouilles, ont étendu leur étude à l’ensemble des domus mises au jour lors de fouilles entreprises par la Surintendance à partir des années 1939 et 1941. Ce travail qui répond à l’objectif présenté dans la Chronique 2015, à savoir la reconstruction de la ville d’Arpi à travers ..

Antibiotics or No Antibiotics, That Is the Question: An Update on Efficient and Effective Use of Antibiotics in Dental Practice

The antimicrobial resistance (AMR) phenomenon is an emerging global problem and is induced by overuse and misuse of antibiotics in medical practice. In total, 10% of antibiotic prescriptions are from dentists, usually to manage oro-dental pains and avoid postsurgical complications. Recent research and clinical evaluations highlight new therapeutical approaches with a reduction in dosages and number of antibiotic prescriptions and recommend focusing on an accurate diagnosis and improvement of oral health before dental treatments and in patients' daily lives. In this article, the most common clinical and operative situations in dental practice, such as endodontics, management of acute alveolar abscesses, extractive oral surgery, parodontology and implantology, are recognized and summarized, suggesting possible guidelines to reduce antibiotic prescription and consumption, maintaining high success rates and low complications rates. Additionally, the categories of patients requiring antibiotic administration for pre-existing conditions are recapitulated. To reduce AMR threat, it is important to establish protocols for treatment with antibiotics, to be used only in specific situations. Recent reviews demonstrate that, in dentistry, it is possible to minimize the use of antibiotics, thoroughly assessing patient's conditions and type of intervention, thus improving their efficacy and reducing the adverse effects and enhancing the modern concept of personalized medicine

Epstein–Barr Virus in Salivary Samples from Systemic Lupus Erythematosus Patients with Oral Lesions

In order to investigate the possible role of Epstein–Barr virus (EBV) in systemic lupus erythematosus (SLE) and its associated oral lesions, a pilot case–control study was performed. A total of 31 patients (18 females and 13 males) were enrolled in the study and divided into two groups: group A included 16 patients with diagnosis of SLE and group B included 15 healthy individuals. Salivary swab samples were collected and subjected to molecular screening by real-time quantitative PCR (qPCR) for the detection of EBV DNA. EBV DNA was significantly detected in 8/16 (50%) SLE patients and in 5/7 (71.4%) subjects with SLE-associated oral lesions. Since EBV is one of the most common viruses in the human population, it is difficult to understand if it is the causative agent of SLE or, vice versa, if SLE is able to trigger the reactivation of EBV. This study highlights a significant association between the presence of EBV and both SLE and SLE-related oral lesions and provides rationale for further investigation into the role of EBV in SLE pathogenesi

Tumor necrosis factor‑α in systemic lupus erythematosus: Structure, function and therapeutic implications (Review)

: Tumor necrosis factor‑α (TNF‑α) is a pleiotropic pro‑inflammatory cytokine that contributes to the pathophysiology of several autoimmune diseases, such as multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus (SLE). The specific role of TNF‑α in autoimmunity is not yet fully understood however, partially, in a complex disease such as SLE. Through the engagement of the TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2), both the two variants, soluble and transmembrane TNF‑α, can exert multiple biological effects according to different settings. They can either function as immune regulators, impacting B‑, T‑ and dendritic cell activity, modulating the autoimmune response, or as pro‑inflammatory mediators, regulating the induction and maintenance of inflammatory processes in SLE. The present study reviews the dual role of TNF‑α, focusing on the different effects that TNF‑α may have on the pathogenesis of SLE. In addition, the efficacy and safety of anti‑TNF‑α therapies in preclinical and clinical trials SLE are discussed

INFANT GROWTH DURING THE FIRST YEAR OF LIFE

Objective: The aim of this study was to describe and analyse the profile of growth in normal infants during the first year of life, including their patterns of weight and length, and the duration of breastfeeding. Methods: This is a retrospective cohort study conducted based on 85 records of infants who met the inclusion criteria. The total duration of breastfeeding was recorded along with weight and length at three ages: birth, 6 and 12 months. The data were analysed as Z-scores based on WHO (2006) using the software products MedCalc 12.0 and GraphPad Prism 6.0. Results: Although 76.5% of the infants showed a growth pattern compatible with WHO references at 12 months of age, the others presented as overweight as at risk of being overweight. A significant correlation was observed between birth weight and BMI Z-score at two ages: 6 months (r = 0.26; p = 0.01) and 12 months (r = 0.32; p = 0.002). A correlation between birth weight and length Z-score was also found at 6 months (r = 0.4034; p = 0.0001) and 12 months (r = 0.3309; p = 0.002). Birth length was also correlated with length Z-score at 6 months (r = 0.4829; p<0.0001) and 12 months (r = 0.3407; p = 0.0014). Breastfeeding duration did not show any correlation with anthropometric data at 6 and 12 months of age. Conclusion: The growth pattern of the sample during the first year of life was found to be appropriate or faster than normal. Growth pattern also seems to be influenced by anthropometric characteristics at birth, which does not depend on breastfeeding duration

Arpi. Formes et modes de vie d’une cité italiote (IVe-IIe siècle av. n.è.)

Le texte de ces Chroniques présente la troisième et dernière étape préliminaire du programme de recherches sur Arpi : formes et modes de vie d’une cité italiote, qui a débuté en 2014 et vise à produire une synthèse sur les formes de l’habitat d’époque hellénistique. La double particularité du projet se reflète dans la composition de cette contribution : il prend appui, d’une part, sur l’étude topographique, stratigraphique et matérielle, des données de fouilles anciennes conduites sous la responsabilité de la Surintendance entre le début de la seconde guerre mondiale et la fin des années 1990, d’autre part sur la mise à jour des découvertes dans une base géoréférencée, sur une enquête d’archéologie des paysages, avec une approche archéomorphologique, géomorphologique et géophysique, et sur des prospections pédestres. La recontextualisation qui en résulte n’est possible que grâce à la complémentarité des expériences et des compétences réunies par la Surintendance des Pouilles, puis de Foggia, du Centre Jean Bérard et de l’Université de Salerne. Elle a été conduite à plusieurs échelles, de la maison au territoire, pour mieux définir les contraintes, les ressources et l’évolution du paysage au sein duquel s’est développé ce phénomène urbain de très grande envergure et encore difficile à cerner sur l’ensemble de l’espace limité par l’agger

Arpi. Formes et modes de vie d’une cité italiote (ive‑iie siècle av. n. è.) – Campagne d’étude 2022

Données scientifiques produites : Arpi. Formes et modes de vie d’une cité italiote Chroniques de l’EFR :https://journals.openedition.org/cefr/1641 Introduction Le nouveau volet ouvert en 2020 sur l’aire de l’Hypogée de la Méduse a été approfondi cette année grâce à trois missions de documentation dans les dépôts de la Surintendance, via Arpi (15‑18 mars, 15‑19 mai, 12‑15 juillet 2022). Ce secteur situé au SO du site est bien connu par la présence d’un ensemble de tombes à chambres publiées ..

Dendritic cell vaccination in metastatic melanoma turns \u201cnon-T cell inflamed\u201d into \u201cT-cell inflamed\u201d tumors

Dendritic cell (DC)-based vaccination effectively induces anti-tumor immunity, although in the majority of cases this does not translate into a durable clinical response. However, DC vaccination is characterized by a robust safety profile, making this treatment a potential candidate for effective combination cancer immunotherapy. To explore this possibility, understanding changes occurring in the tumor microenvironment (TME) upon DC vaccination is required. In this line, quantitative and qualitative changes in tumor-infiltrating T lymphocytes (TILs) induced by vaccination with autologous tumor lysate/homogenate loaded DCs were investigated in a series of 16 patients with metastatic melanoma. Immunohistochemistry for CD4, CD8, Foxp3, Granzyme B (GZMB), PDL1, and HLA class I was performed in tumor biopsies collected before and after DC vaccination. The density of each marker was quantified by automated digital pathology analysis on whole slide images. Co-expression of markers defining functional phenotypes, i.e., Foxp3+ regulatory CD4+ T cells (Treg) and GZMB+ cytotoxic CD8+ T cells, was assessed with sequential immunohistochemistry. A significant increase of CD8+ TILs was found in post-vaccine biopsies of patients who were not previously treated with immune-modulating cytokines or Ipilimumab. Interestingly, along with a maintained tumoral HLA class I expression, after DC vaccination we observed a significant increase of PDL1+ tumor cells, which significantly correlated with intratumoral CD8+ T cell density. This observation might explain the lack of a significant concurrent cytotoxic reactivation of CD8+ T cell, as measured by the numbers of GZMB+ T cells. Altogether these findings indicate that DC vaccination exerts an important role in sustaining or de novo inducing a T cell inflamed TME. However, the strength of the intratumoral T cell activation detected in post-DC therapy lesions is lessened by an occurring phenomenon of adaptive immune resistance, yet the concomitant PDL1 up-regulation. Overall, this study sheds light on DC immunotherapy-induced TME changes, lending the rationale for the design of smarter immune-combination therapies