Search results for "EFFECTOR"
showing 10 items of 217 documents
Research in practice: The impact of interferon-α therapy on immune tolerance
2014
Interferon-α (IFN-α) is the only drug approved for adjuvant therapy of malignant melanoma and is also used in the treatment of hematological and solid tumors. Along with its proven clinical efficacy, IFN-α produces several side effects, particularly with regard to autoimmune disorders. Curious about symptoms of autoimmunity during IFN-α therapy, we asked whether IFN-α directly impacts on immune tolerance. We found that IFN-α does alter the function of tolerogenic dendritic cells (DC) as well as of induced and naturally occurring T-regulatory cells (nTregs). IFN-α blocks the tolerogenic phenotype of DC by inducing maturation and thus preventing the induction of inducible Tregs by DC. It also…
The role of death effector domain (DED)-containing proteins in acute oxidative cell injury in hepatocytes
2012
Abstract Apoptosis is a mechanism that regulates hepatic tissue homeostasis and contributes to both acute and chronic injury in liver disease. The apoptotic signaling cascade involves activation of the death-inducing signaling complex (DISC) and subsequent recruitment of proteins containing death effector domains (DED), which regulate downstream effector molecules. Prominent among these are the Fas-associated death domain (FADD) and the cellular caspase 8-like inhibitory protein (cFLIP), and alterations in these proteins can lead to severe disruption of physiological processes, including acute liver failure or hepatocellular carcinoma. Their role in cell signaling events independent of the …
Regulating TRAIL Receptor-Induced Cell Death at the Membrane: A Deadly Discussion
2011
Article Open access plus; International audience; The use of TRAIL/APO2L and monoclonal antibodies targeting TRAIL receptors for cancer therapy holds great promise, due to their ability to restore cancer cell sensitivity to apoptosis in association with conventional chemotherapeutic drugs in a large variety of tumors. TRAIL-induced cell death is tightly regulated right from the membrane and at the DISC (Death-Inducing Signaling Complex) level. The following patent and literature review aims to present and highlight recent findings of the deadly discussion that determines tumor cell fate upon TRAIL engagement.
Evolutionary Dissection of the Dot/Icm System Based on Comparative Genomics of 58 Legionella Species
2019
14 páginas, 2 figuras, 2 tablas
4-Dechloro-14-deoxy-oxacyclododecindione and 14-deoxy-oxacylododecindione, two inhibitors of inducible connective tissue growth factor expression fro…
2015
Connective tissue growth factor (CTGF/CCN2), a member of the CCN superfamily of secreted cysteine-rich glycoproteins, is a central mediator of tissue remodeling and fibrosis. CTGF is suggested to be an important down-stream effector of transforming growth factor-beta (TGF-β) signaling and has therefore reached considerable pathophysiological relevance because of its involvement in the pathogenesis of fibrotic diseases, atherosclerosis, skin scarring, and other conditions with excess production of connective tissue. In a search for inhibitors of inducible CTGF expression from fungi, two new macrocyclic lactones, namely 4-dechloro-14-deoxy-oxacyclododecindione (1) and 14-deoxy-oxacylododecind…
Wnt3a Neutralization Enhances T-cell Responses through Indirect Mechanisms and Restrains Tumor Growth
2018
Abstract The Wnt/β-catenin pathway regulates T-cell functions, including the repression of effector functions to the advantage of memory development via Tcf1. In a companion study, we demonstrate that, in human cancers, Wnt3a/β-catenin signaling maintains tumor-infiltrating T cells in a partially exhausted status. Here, we have investigated the effects of Wnt3a neutralization in vivo in a mouse tumor model. Abundant Wnt3a was released, mostly by stromal cells, in the tumor microenvironment. We tested whether Wnt3a neutralization in vivo could rescue the effector capacity of tumor-infiltrating T cells, by administering an antibody to Wnt3a to tumor-bearing mice. This therapy restrained tumor…
Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy
2016
Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encod…
Diminished Contact Hypersensitivity Response in IL‐4 Deficient Mice at a Late Phase of the Elicitation Reaction
1997
Contact hypersensitivity (CHS) is thought to depend on the activation of T cells of Th1 and/or Tc1 type. The role of Th2/Tc2 cells in the contact allergic reaction is not clear. The aim of this study was to analyse the functional contribution of Th2/Tc2 cells in CHS using the interleukin-4 (IL-4) deficient mouse model. Interleukin-4 deficient (IL4T) and control (wt) mice were sensitized by epicutaneous application of 2,4-dinitrofluorobenzene. The ear swelling response measured 24 h after challenge was similar in IL4T and control mice. However, from 48 h onwards, ear swelling values were significantly reduced in IL4T mice. The stimulatory capacity of freshly isolated as well as 3-day culture…
Nucleoside phosphotransferase in animal tissues. Tissue distribution and kinetic properties
1985
Amphibian, avian and mammal tissues contain a nucleoside phosphotransferase clearly different from those previously described in vegetables and bacteria. Whatever the animal source, the enzyme showed many similar characteristics as far as substrate specificity, dependence upon Mg2+, instability at 37 degrees C, and the protecting effect of nucleotides were concerned. Moreover, when submitted to gel filtration, the enzyme behaved in all cases as a dissociable high molecular weight protein, whose degree of association was controlled by nucleotides. In amphibian and avian tissues multiple forms of the enzyme seem to be present which differ for the substrate concentration at half-maximal veloci…
Analysis of memory and effector CD8+ T cell subsets in chronic graft-versus-host disease.
2009
In humans, the selective depletion of CD8+ cells may prevent GVHD after allogeneic transplantation. These cells can infiltrate and damage target tissues. It is of interest to investigate the phenotypical characteristics and cytotoxic properties of the different CD8+ subsets in cGVHD patients. In a preliminary study we found that patients with cGVHD had a markedly elevated percentage of peripheral blood CCR7−/CD45RA+ cells compared to patients without cGVHD; conversely, the CCR7+/CD45RA+ subsets of CD8+ cells was significantly decreased. In this study, we report in depth on the phenotype of effector T cell subsets in cGVHD patients, as well as their proliferative capability, cytotoxic prope…