Search results for "81.60"

CD40 activity on mesenchymal cells negatively regulates OX40L to maintain bone marrow immune homeostasis under stress conditions

2021

BackgroundWithin the bone marrow (BM), mature T cells are maintained under homeostatic conditions to facilitate proper hematopoietic development. This homeostasis depends upon a peculiar elevated frequency of regulatory T cells (Tregs) and immune regulatory activities from BM-mesenchymal stem cells (BM-MSCs). In response to BM transplantation (BMT), the conditioning regimen exposes the BM to a dramatic induction of inflammatory cytokines and causes an unbalanced T-effector (Teff) and Treg ratio. This imbalance negatively impacts hematopoiesis, particularly in regard to B-cell lymphopoiesis that requires an intact cross-talk between BM-MSCs and Tregs. The mechanisms underlying the ability of…

Enhancing the Activation and Releasing the Brakes: A Double Hit Strategy to Improve NK Cell Cytotoxicity Against Multiple Myeloma

2018

Natural killer (NK) cells are innate lymphocytes with a strong antitumor ability. In tumor patients, such as multiple myeloma (MM) patients, an elevated number of NK cells after stem cell transplantation (SCT) has been reported to be correlated with a higher overall survival rate. With the aim of improving NK cell use for adoptive cell therapy, we also addressed the cytotoxicity of patient-derived, cytokine-stimulated NK cells against MM cells at specific time points: at diagnosis and before and after autologous stem cell transplantation. Remarkably, after cytokine stimulation, the patients' NK cells did not significantly differ from those of healthy donors. In a small cohort of MM patients…

Real-world experience with dupilumab in severe asthma: One-year data from an italian named patient program

2021

Raffaele Campisi,1 Claudia Crimi,1 Santi Nolasco,2 Bianca Beghè,3 Leonardo Antonicelli,4 Gabriella Guarnieri,5 Nicola Scichilone,6 Morena Porto,2 Luigi Macchia,7 Giulia Scioscia,8 Maria Pia Foschino Barbaro,8 Alberto Papi,9 Nunzio Crimi1,2 1Respiratory Medicine Unit, A.O.U. Policlinico “G. Rodolico -San Marco”, Catania, Italy; 2Department of Clinical and Experimental Medicine, Section of Respiratory Diseases, University of Catania, Catania, Italy; 3Respiratory Medicine Unit, Department of Medicine, University of Modena and Reggio Emilia, Modena, Italy; 4Allergy Unit, Department of Internal Medicine, Ancona University Hospital, Ancona, Italy; 5Department of Car…

Dexamethasone premedication suppresses vaccine-induced immune responses against cancer

2020

ABSTRACT Glucocorticosteroids (GCS) have an established role in oncology and are administered to cancer patients in routine clinical care and in drug development trials as co-medication. Given their strong immune-suppressive activity, GCS may interfere with immune-oncology drugs. We are developing a therapeutic cancer vaccine, which is based on a liposomal formulation of tumor-antigen encoding RNA (RNA-LPX) and induces a strong T-cell response both in mice as well as in humans. In this study, we investigated in vivo in mice and in human PBMCs the effect of the commonly used long-acting GCS Dexamethasone (Dexa) on the efficacy of this vaccine format, with a particular focus on antigen-specif…

Editorial: Thymic Epithelial Cells: New Insights Into the Essential Driving Force of T-Cell Differentiation.

2021

CVB3 VP1 interacts with MAT1 to inhibit cell proliferation by interfering with Cdk-activating kinase complex activity in CVB3-induced acute pancreati…

2021

Coxsackievirus B3 (CVB3) belongs to the genus Enterovirus of the family Picornaviridae and can cause acute acinar pancreatitis in adults. However, the molecular mechanisms of pathogenesis underlying CVB3-induced acute pancreatitis have remained unclear. In this study, we discovered that CVB3 capsid protein VP1 inhibited pancreatic cell proliferation and exerted strong cytopathic effects on HPAC cells. Through yeast two-hybrid, co-immunoprecipitation, and confocal microscopy, we show that Menage a trois 1 (MAT1), a subunit of the Cdk-Activating Kinase (CAK) complex involved in cell proliferation and transcription, is a novel interaction protein with CVB3 VP1. Moreover, CVB3 VP1 inhibited MAT…

Infection-induced chromatin modifications facilitate translocation of herpes simplex virus capsids to the inner nuclear membrane

2021

Herpes simplex virus capsids are assembled and packaged in the nucleus and move by diffusion through the nucleoplasm to the nuclear envelope for egress. Analyzing their motion provides conclusions not only on capsid transport but also on the properties of the nuclear environment during infection. We utilized live-cell imaging and single-particle tracking to characterize capsid motion relative to the host chromatin. The data indicate that as the chromatin was marginalized toward the nuclear envelope it presented a restrictive barrier to the capsids. However, later in infection this barrier became more permissive and the probability of capsids to enter the chromatin increased. Thus, although …

Immune responses during COVID-19 infection

2020

International audience; Over the past 16 years, three coronaviruses (CoVs), severe acute respiratory syndrome CoV (SARS-CoV) in 2002, Middle East respiratory syndrome CoV (MERS-CoV) in 2012 and 2015, and SARS-CoV-2 in 2020, have been causing severe and fatal human epidemics. The unpredictability of coronavirus disease-19 (COVID-19) poses a major burden on health care and economic systems across the world. This is caused by the paucity of in-depth knowledge of the risk factors for severe COVID-19, insufficient diagnostic tools for the detection of SARS-CoV-2, as well as the absence of specific and effective drug treatments. While protective humoral and cellular immune responses are usually m…