Search results for "CD"

Time to activin on pathogenic T cells

2020

In multiple sclerosis (MS), Th17 cells are critical drivers of autoimmune central nervous system (CNS) inflammation and demyelination. Th17 cells exhibit functional heterogeneity fostering both pathogenic and nonpathogenic, tissue-protective functions. Still, the factors that control Th17 pathogenicity remain incompletely defined. Here, using experimental autoimmune encephalomyelitis, an established mouse MS model, we report that therapeutic administration of activin-A ameliorates disease severity and alleviates CNS immunopathology and demyelination, associated with decreased activation of Th17 cells. In fact, activin-A signaling through activin-like kinase-4 receptor represses pathogenic t…

Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression.

2017

Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial muc…

Activation and selective IL-17 response of human Vγ9Vδ2 T lymphocytes by TLR-activated plasmacytoid dendritic cells.

2016

// Elena Lo Presti 1,2 , Nadia Caccamo 1,2 , Valentina Orlando 1,2 , Francesco Dieli 1,2 and Serena Meraviglia 1,2 1 Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, Palermo, Italy 2 Department of Biopathology and Medical Biotechnologies (DIBIMED), University of Palermo, Palermo, Italy Correspondence to: Serena Meraviglia, email: // Keywords : γδ T cells, plasmacytoid dendritic cells, IL-17, TLR activation, proliferation, Immunology and Microbiology Section, Immune response, Immunity Received : July 20, 2016 Accepted : August 02, 2016 Published :August 31, 2016 Abstract Vγ9Vδ2 T cells and plasmacytoid dendritic cells (pDCs) are two distinc…

Cellular and Molecular Mechanisms of Fat Taste Perception

2021

During the last couples of years, a number of studies have increasingly accumulated on the gustatory perception of dietary fatty acids in rodent models and human beings in health and disease. There is still a debate to coin a specific term for the gustatory perception of dietary fatty acids either as the sixth basic taste quality or as an alimentary taste. Indeed, the psycho-physical cues of orosensory detection of dietary lipids are not as distinctly perceived as other taste qualities like sweet or bitter. The cellular and molecular pharmacological mechanisms, triggered by the binding of dietary long-chain fatty acids (LCFAs) to tongue taste bud lipid receptors like CD36 and GPR120, involv…

Cytomegalovirus vector expressing RAE-1γ induces enhanced anti-tumor capacity of murine CD8+ T cells

2017

Designing of CD8 T cell vaccines which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show a robust potential of a cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8 T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1. Expression of RAE-1γ by the CMV vector potentiated expansion of KLRG1+ CD8 T cells wi…

Characterisation of CDKL5 Transcript Isoforms in Human and Mouse.

2016

Mutations in the X-linked Cyclin-Dependent Kinase-Like 5 gene (CDKL5) cause early onset infantile spasms and subsequent severe developmental delay in affected children. Deleterious mutations have been reported to occur throughout the CDKL5 coding region. Several studies point to a complex CDKL5 gene structure in terms of exon usage and transcript expression. Improvements in molecular diagnosis and more extensive research into the neurobiology of CDKL5 and pathophysiology of CDKL5 disorders necessitate an updated analysis of the gene. In this study, we have analysed human and mouse CDKL5 transcript patterns both bioinformatically and experimentally. We have characterised the predominant brai…

GDF11 exhibits tumor suppressive properties in hepatocellular carcinoma cells by restricting clonal expansion and invasion.

2019

Growth differentiation factor 11 (GDF11) has been characterized as a key regulator of differentiation in cells that retain stemness features, despite some controversies in age-related studies. GDF11 has been poorly investigated in cancer, particularly in those with stemness capacity, such as hepatocellular carcinoma (HCC), one of the most aggressive cancers worldwide. Here, we focused on investigating the effects of GDF11 in liver cancer cells. GDF11 treatment significantly reduced proliferation, colony and spheroid formation in HCC cell lines. Consistently, down-regulation of CDK6, cyclin D1, cyclin A, and concomitant upregulation of p27 was observed after 24 h of treatment. Interestingly,…

AC‐1001 H3 CDR peptide induces apoptosis and signs of autophagy in vitro and exhibits antimetastatic activity in a syngeneic melanoma model

2016

Antibody-derived peptides modulate functions of the immune system and are a source of anti-infective and antitumor substances. Recent studies have shown that they comprise amino acid sequences of immunoglobulin complementarity-determining regions, but also fragments of constant regions. VH CDR3 of murine mAb AC-1001 displays antimetastatic activities using B16F10-Nex2 murine melanoma cells in a syngeneic model. The peptide was cytotoxic in vitro in murine and human melanoma cells inducing reactive oxygen species (ROS) and apoptosis by the intrinsic pathway. Signs of autophagy were also suggested by the increased expression of LC3/LC3II and Beclin 1 and by ultrastructural evidence. AC-1001 H…

2018

AbstractThe cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells with CRISPR/Cas9-engineered CDH1 mutations, we identified synthetic lethality between E-cadherin deficiency and inhibition of the tyrosine kinase ROS1. Data from large-scale genetic screens in molecularly diverse breast tumor cell lines established that the E-cadherin/ROS1 synthetic lethality was not only robust in the face of considerable molecular heterogeneity but was also elicited with clinical ROS1 inhibitors, including foretinib and crizotinib. ROS1 inhibitor…

2020

Background: The spontaneous preference for dietary fat is regulated by two lingual lipid sensors (CD36 and GPR120) in humans and rodents. Our objective was to investigate whether obesity in children is associated with methylation of lipid sensor genes, and whether this alteration was implicated in altered gustatory perception of fat and bitter and increased preference of palatable foods. Methods: School children were recruited and classified according to their body mass index (BMI) z-score into two groups: obese and lean children. The detection of orosensory perception for oleic acid and 6-n-propylthiouracil was assessed by using a 3-alternative forced-choice test. After blood DNA extractio…