A5074855850- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Immune cells in cancer
- Extracellular vesicles in disease
- CAR-T cell therapy research
- IL-33, ST2, and ILC Pathways
- RNA regulation and disease
- Inflammasome and immune disorders
- Virus-based gene therapy research
- HIV Research and Treatment
- T-cell and Retrovirus Studies
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- interferon and immune responses
- Aquaculture disease management and microbiota
- Adipose Tissue and Metabolism
- Immune Response and Inflammation
- Protein Tyrosine Phosphatases
- Peptidase Inhibition and Analysis
- Cancer Immunotherapy and Biomarkers
- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- Cytomegalovirus and herpesvirus research
Universidad Complutense de Madrid
2024
Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
2024
Universidad Autónoma de Madrid
2008-2022
Consejo Superior de Investigaciones Científicas
2008-2022
Center for Cancer Research
2018-2022
National Cancer Institute
2018-2022
Centro de Biología Molecular Severo Ochoa
2008-2022
National Institutes of Health
2015-2020
National Institute of Allergy and Infectious Diseases
2015-2019
Boston Psychoanalytic Society and Institute
2013
Significance Previously we demonstrated that IL-15 by continuous infusion at 2 μg/kg/d for 10 days induced a 38-fold increase in circulating natural killer (NK) cells and 358-fold CD56 bright NK cells. In the present study enhanced antibody-dependent cellular cytotoxicity (ADCC) of tumor-directed monoclonal antibodies two systems. Both macrophages were required optimal therapeutic responses. These studies support clinical trials combined with antibodies. translation this study, phase I trial...
T cell antigen receptor–proximal signaling components, Rho-family GTPases, and formin proteins DIA1 FMNL1 have been implicated in centrosome reorientation to the immunological synapse of lymphocytes. However, role these molecules process is not yet defined. Here we find that a subset microtubules became rapidly stabilized their α-tubulin subunit posttranslationally detyrosinated after engagement receptor. Formation stabilized, required INF2, which was also found be essential for...
The MAL protein is an essential component of the specialized machinery for apical targeting in epithelial cells. src family kinase Lck plays a pivotal role T cell signaling. We show that required cells efficient expression at plasma membrane and activation IL-2 transcription. To investigate mechanism by which regulates targeting, we analyzed dynamics found it travels to specific transport carriers containing MAL. Coimmunoprecipitation experiments indicated association with Lck. Both carrier...
T cell membrane receptors and signaling molecules assemble at the immunological synapse (IS) in a supramolecular activation cluster (SMAC), organized into two differentiated subdomains: central SMAC (cSMAC), with TCR, Lck, linker for of cells (LAT), peripheral (pSMAC), adhesion molecules. The mechanism protein sorting to subdomains is still unknown. MAL forms part machinery targeting plasma by specialized mechanisms involving condensed membranes or rafts. In this article, we report our...
Interleukin 15 (IL-15) is an essential cytokine for the survival and proliferation of natural killer (NK) cells. IL-15 activates signaling by β common γ (γc) chain heterodimer IL-2 receptor through trans-presentation cells expressing bound to α (IL-15Rα). We show here that membrane-associated IL-15Rα-IL-15 complexes are transferred from presenting NK trans-endocytosis contribute phosphorylation ribosomal protein S6 cell proliferation. interaction with soluble or surface-bound complex...
Abstract Exosomes secreted by T cells play an important role in coordinating the immune response. HIV-1 Nef hijacks route of exosome secretion to modulate functioning uninfected cells. Despite importance process, protein machinery involved biogenesis is yet be identified. In this study, we show that MAL, a tetraspanning membrane expressed human cells, present endosomes travel toward plasma for secretion. absence release particles and markers was greatly impaired. This effect accompanied...
IL-15 bound to the IL-15Rα-chain (IL-15Rα) is presented in trans cells bearing IL-2Rβ-chain and common γ-chain. As transpresentation occurs context of cell-to-cell contacts, it has potential for regulation by other receptor-ligand interactions. In this study, human NK were tested sensitivity inhibitory receptors. Human expressing HLA class I ligands receptors KIR2DL1, KIR2DL2/3, or CD94-NKG2A transfected with IL-15Rα. Proliferation primary response transpresented was reduced engagement...
T-cell antigen receptor (TCR) engagement triggers the rapid reorientation of centrosome, which is associated with secretory machinery, towards immunological synapse (IS) for polarized protein trafficking. Recent evidence indicates that upon TCR triggering INF2 formin, together formins DIA1 and FMNL1, promotes formation a specialized array stable detyrosinated MTs breaks symmetrical organization microtubule (MT) cytoskeleton. The MT TCR-induced tyrosine phosphorylation should coincide...
Natural Killer (NK) cells mediate mainly innate anti-tumor and anti-viral immune responses respond to a variety of cytokines other stimuli promote survival, cellular proliferation, production such as interferon gamma (IFNγ) and/or cytotoxicity programs. NK cell activation by cytokine stimulation requires substantial remodeling metabolic pathways support their bioenergetic biosynthetic requirements. There is large body evidence that suggests impaired metabolism associated with number chronic...
Cancer-associated fibroblasts (CAFs) are the most abundant stromal cellular component in tumor microenvironment (TME). CAFs contribute to tumorigenesis and have been proposed as targets for anticancer therapies. Similarly, dysregulation of SUMO machinery components can disrupt balance SUMOylation, contributing drug resistance various cancers, including breast cancer. We explored role SUMOylation evaluated its potential a therapeutic strategy used pharmacological genetic approaches analyse...
Natural Killer (NK) cells mediate mainly innate anti-tumor and anti-viral immune responses respond to a variety of cytokines other stimuli promote survival, cellular proliferation, production such as interferon gamma (IFNγ) and/or cytotoxicity programs. NK cell activation by cytokine stimulation requires substantial remodeling metabolic pathways support their bioenergetic biosynthetic requirements. There is large body evidence that suggests impaired metabolism associated with number chronic...