Search results for "Transduction"
showing 10 items of 2149 documents
Osteoclast Immunosuppressive Effects in Multiple Myeloma: Role of Programmed Cell Death Ligand 1
2018
Immunomodulatory drugs and monoclonal antibody-based immunotherapies have significantly improved the prognosis of the patients with multiple myeloma (MM) in the recent years. These new classes of reagents target malignant plasma cells (PCs) and further modulate the immune microenvironment, which prolongs anti-MM responses and may prevent tumor occurrence. Since MM remains an incurable cancer for most patients, there continues to be a need to identify new tumor target molecules and investigate alternative cellular approaches using gene therapeutic strategies and novel treatment mechanisms. Osteoclasts (OCs), as critical multi-nucleated large cells responsible for bone destruction in >80% …
Editorial: Understanding Gamma Delta T Cell Multifunctionality - Towards Immunotherapeutic Applications.
2020
Introduction: gd T cells have been characterized by the expression of a gd T cell receptor (TCR).When the gd TCR and the corresponding ab TCR were first discovered it was assumed that the corresponding cell types were likely to be functionally very similar. However, some 30 years later, we have realized that they are not. Unlike ab T cells, gd T cells (i) sense target antigens independent of MHC molecules; (ii) display NK-cell like innate reactivities, including killing of infected cells as well as microbes; (iii) are able to take up large particulates, including bacteria, and (iv) can act as professional antigen presenting cells. The “stress sensing” abilities of gd T cells have led to a g…
Genome-Wide Inhibition of Pro-atherogenic Gene Expression by Multi-STAT Targeting Compounds as a Novel Treatment Strategy of CVDs.
2018
Cardiovascular diseases (CVDs), including atherosclerosis, are globally the leading cause of death. Key factors contributing to onset and progression of atherosclerosis include the pro-inflammatory cytokines Interferon (IFN)a and IFN? and the Pattern Recognition Receptor (PRR) Toll-like receptor 4 (TLR4). Together, they trigger activation of Signal Transducer and Activator of Transcription (STAT)s. Searches for compounds targeting the pTyr-SH2 interaction area of STAT3, yielded many small molecules, including STATTIC and STX-0119. However, many of these inhibitors do not seem STAT3-specific. We hypothesized that multi-STAT-inhibitors that simultaneously block STAT1, STAT2, and STAT3 activit…
IL-12 Expands and Differentiates Human Vγ2Vδ2 T Effector Cells Producing Antimicrobial Cytokines and Inhibiting Intracellular Mycobacterial Growth
2019
While IL-12 plays a key role in differentiation of protective CD4+ Th1 response, little is known about mechanisms whereby IL-12 differentiates other T-cell populations. Published studies suggest that predominant Vγ2Vδ2 T cells in humans/nonhuman primates (NHP) are a fast-acting T-cell subset, with capacities to rapidly expand and produce Th1 and cytotoxic cytokines in response to phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) produced by Mycobacterium tuberculosis (Mtb) or others. However, whether IL-12 signaling pathway mediates fast-acting and Th1 or anti-microbial features of Vγ2Vδ2 T cells remains poorly defined. Here, we show that IL-12, but not other IL-12 fami…
Are Toll-like receptors and decoy receptors involved in the immunopathogenesis of systemic lupus erythematosus and lupus-like syndromes?
2011
In this paper we focus our attention on the role of two families of receptors, Toll-like receptors (TLR) and decoy receptors (DcR) involved in the generation of systemic lupus erythematosus (SLE) and lupus-like syndromes in human and mouse models. To date, these molecules were described in several autoimmune disorders such as rheumatoid arthritis, antiphospholipids syndrome, bowel inflammation, and SLE. Here, we summarize the findings of recent investigations on TLR and DcR and their role in the immunopathogenesis of the SLE.
Prediction of Specific TCR-Peptide Binding From Large Dictionaries of TCR-Peptide Pairs
2019
Abstract The T cell repertoire is composed of T cell receptors (TCR) selected by their cognate MHC-peptides and naive TCR that do not bind known peptides. While the task of distinguishing a peptide-binding TCR from a naive TCR unlikely to bind any peptide can be performed using sequence motifs, distinguishing between TCRs binding different peptides requires more advanced methods. Such a prediction is the key for using TCR repertoires as disease-specific biomarkers. We here used large scale TCR-peptide dictionaries with state-of-the-art natural language processing (NLP) methods to produce ERGO (pEptide tcR matchinG predictiOn), a highly specific classifier to predict which TCR binds to which…
New Insight into Immunity and Immunopathology of Rickettsial Diseases
2011
Human rickettsial diseases comprise a variety of clinical entities caused by microorganisms belonging to the generaRickettsia,Orientia,Ehrlichia, andAnaplasma. These microorganisms are characterized by a strictly intracellular location which has, for long, impaired their detailed study. In this paper, the critical steps taken by these microorganisms to play their pathogenic roles are discussed in detail on the basis of recent advances in our understanding of molecularRickettsia-host interactions, preferential target cells, virulence mechanisms, three-dimensional structures of bacteria effector proteins, upstream signalling pathways and signal transduction systems, and modulation of gene exp…
The NG2 Proteoglycan Protects Oligodendrocyte Precursor Cells against Oxidative Stress via Interaction with OMI/HtrA2.
2015
The NG2 proteoglycan is characteristically expressed by oligodendrocyte progenitor cells (OPC) and also by aggressive brain tumours highly resistant to chemo- and radiation therapy. Oligodendrocyte-lineage cells are particularly sensitive to stress resulting in cell death in white matter after hypoxic or ischemic insults of premature infants and destruction of OPC in some types of Multiple Sclerosis lesions. Here we show that the NG2 proteoglycan binds OMI/HtrA2, a mitochondrial serine protease which is released from damaged mitochondria into the cytosol in response to stress. In the cytosol, OMI/HtrA2 initiates apoptosis by proteolytic degradation of anti-apoptotic factors. OPC in which NG…
EGF-Induced Acetylation of Heterogeneous Nuclear Ribonucleoproteins Is Dependent on KRAS Mutational Status in Colorectal Cancer Cells.
2015
KRAS mutational status is considered a negative predictive marker of the response to anti-EGFR therapies in colorectal cancer (CRC) patients. However, conflicting data exist regarding the variable response to EGFR-targeted therapy. The effects of oncogenic KRAS on downstream targets were studied in cell lines with different KRAS mutations. Cells harboring a single KRASG13D allele showed the most tumorigenic profile, with constitutive activation of the downstream pathway, rendering them EGF-unresponsive. Conversely, KRASA146T cells showed a full EGF-response in terms of signal transduction pathways, cell proliferation, migration or adhesion. Moreover, the global acetylome of CRC cells was al…
Mucins as a New Frontier in Pulmonary Fibrosis
2019
Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pulmonary disease with a median survival of 3–5 years after diagnosis. Recent evidence identifies mucins as key effectors in cell growth and tissue remodeling processes compatible with the processes observed in IPF. Mucins are classified in two groups depending on whether they are secreted (secreted mucins) or tethered to cell membranes (transmembrane mucins). Secreted mucins (MUC2, MUC5AC, MUC5B, MUC6-8 and MUC19) are released to the extracellular medium and recent evidence has shown that a promoter polymorphism in the secreted mucin MUC5B is associated with IPF risk. Otherwise, transmembrane mucins (MUC1, MUC3,…