Publications by authors named "Rodriguez-Frade J"
Article Synopsis
- - CXCR4 is a chemokine receptor that plays key roles in immune cell movement, organ development, and various diseases, including cancer and HIV-1 infection, with only one blocker, plerixafor, currently used clinically.
- - Recent research shows that when activated by CXCL12, CXCR4 changes its structure, reducing membrane-bound units and forming larger immobile clusters necessary for cells to respond to chemical signals.
- - Using molecular modeling, scientists discovered a compound, AGR1.137, that disrupts these CXCR4 clusters without interfering with CXCL12 binding, effectively blocking cellular response to chemical gradients in laboratory settings.
Article Synopsis
- WHIM syndrome is caused by heterozygous mutations in the CXCR4 gene, leading to severe immunodeficiency due to altered receptor functions.* -
- These mutations affect phosphorylation sites in the CXCR4 receptor, resulting in prolonged activation and hyperactive signaling on the cell surface.* -
- Recent research suggests that mutant WHIM receptors behave differently than normal CXCR4, affecting their roles in both normal physiology and disease processes.*
Article Synopsis
- - Current live-cell imaging techniques enable the observation of biological processes in real-time, offering in-depth insights with high spatial and temporal resolution.
- - TrackAnalyzer, an accessible tool via Fiji and ImageJ, allows for semi-automated single-particle tracking and provides comprehensive motion classification as well as quantitative analysis of diffusion and intensity.
- - The TrackAnalyzer workflow automates detection, tracking, classification, and visualization steps, allowing for batch processing of data to efficiently analyze large sets of temporal images.
Article Synopsis
- Macrophages are crucial immune cells that help maintain tissue health, defend against pathogens, and their function can be influenced by their metabolism.
- The study uses various advanced imaging and biochemical techniques to explore how growth hormone (GH) affects the metabolism of inflamed macrophages.
- Results show that GH reprograms these inflammatory macrophages by reducing their metabolism and enhancing mitochondrial function, indicating that targeting macrophage metabolism could be a new strategy for treating inflammatory diseases.
Article Synopsis
- Sphingolipids, ceramides, and cholesterol are key components of cell membranes that influence how cells signal and move by affecting the fluidity of these membranes.
- The study used various assays and tracking methods to show that the lipid environment impacts the organization and function of the CXCR4 receptor, which is crucial for cell migration toward chemical signals.
- Treatment with bacterial sphingomyelinase led to significant changes in the cell membrane's lipid composition, causing altered receptor dynamics and impaired cell migration despite some retained signaling ability.
Article Synopsis
- The organization of chemokine receptors at the cell membrane is heavily influenced by the actin cytoskeleton, affecting how cells respond to signals.
- The truncated CXCR4 receptor mutant (CXCR4R334X), connected to WHIM syndrome, shows altered behavior, failing to cluster properly and affecting receptor mobility after stimulation with CXCL12.
- The study reveals that CXCR4R334X causes improper actin remodeling due to inadequate activation of β-arrestin1, which can lead to severe immune system issues seen in patients with WHIM syndrome.
Article Synopsis
- SARS-CoV-2 vaccination enhances the immune response, providing insights for developing new vaccines and prevention strategies.
- The study evaluated changes in CD4+ T cell reactivity in healthy donors and convalescent individuals after receiving the BNT162b2 vaccine, showing increased reactivity in vaccinated individuals.
- Despite strong antibody responses, certain peptides did not trigger CD4+ lymphocyte activation, and a notable correlation between pre-vaccination CD4+ response and IgA levels was lost post-vaccination.
Here, we describe a new, simple, highly multiplexed serological test that generates a more complete picture of seroconversion than single antigen-based assays. Flow cytometry is used to detect multiple Ig isotypes binding to four SARS-CoV-2 antigens: the Spike glycoprotein, its RBD fragment (the main target for neutralizing antibodies), the nucleocapsid protein, and the main cysteine-like protease in a single reaction. Until now, most diagnostic serological tests measured antibodies to only one antigen and in some laboratory-confirmed patients no SARS-CoV-2-specific antibodies could be detected.
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- SARS-CoV-2 triggers a strong immune response, which is crucial in determining how severe COVID-19 becomes in patients.
- Analysis of blood samples from 276 patients showed that severe cases were linked to a drop in key immune cells (T, B, and NK cells) and changes in specific immune cell types.
- The study highlights the association between severity and a weakened humoral immune response, with implications for developing new treatment strategies for COVID-19.
Currently, there is a need for reliable tests that allow identification of individuals that have been infected with SARS-CoV-2 even if the infection was asymptomatic. To date, the vast majority of the serological tests for SARS-CoV-2-specific Abs are based on serum detection of Abs to either the viral spike glycoprotein (the major target for neutralizing Abs) or the viral nucleocapsid protein that is known to be highly immunogenic in other coronaviruses. Conceivably, exposure of Ags released from infected cells could stimulate Ab responses that might correlate with tissue damage and, hence, they may have some value as a prognostic indicator.
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- Growth hormone (GH) influences immune responses by altering the behavior of macrophages, key immune cells involved in inflammation.
- In laboratory studies, GH treatment enhances anti-inflammatory gene expression in macrophages and reduces proinflammatory signals, contributing to a more favorable immune response.
- In experiments with mice suffering from colitis, GH overexpression was linked to better inflammation resolution and tissue repair, showcasing GH's potential role in moderating inflammatory conditions.
Article Synopsis
- Chemokine receptors are a type of membrane protein that play a crucial role in various cellular functions, including immune responses and movement, by interacting with specific signaling molecules called chemokines.
- The system is highly complex, involving different structural formations (monomers, dimers, oligomers), tightly regulated expression patterns, and the ability of ligands to bind to multiple receptors.
- New imaging technologies are revealing the dynamic changes in receptor shapes that influence how cells respond to chemokines, presenting both challenges and opportunities for developing new drugs.
The Role of the CXCL12/CXCR4/ACKR3 Axis in Autoimmune Diseases.
Front Endocrinol (Lausanne)
August 2019
Article Synopsis
- Chemokine receptors, especially CXCR4, are crucial for regulating cell movement and positioning in various physiological processes and diseases, including embryogenesis and immune responses.
- CXCR4 is known for its unique ligand, SDF1 (CXCL12), and its interaction with ACKR3, making it a key player in tumor progression and autoimmune diseases.
- The CXCL12/CXCR4/ACKR3 signaling pathway presents a promising therapeutic target for inflammatory conditions, with AMD3100 being the only notable antagonist showing clinical significance.
Vasoactive Intestinal Peptide (VIP) is an important immunomodulator of CD4 cells in normal and pathological conditions, which exerts its anti-inflammatory and immunomodulatory actions through VPAC receptors, VPAC and VPAC. Only a decrease in the expression of VPAC mRNA on Th cells upon activation has been reported. Thus, the deepening in the knowledge of the behavior of these receptors may contribute to the design of new therapies based on their activation and/or blockade.
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- The article outlines a method for tracking particles in fluorescence microscopy videos, focusing on cell membrane receptor clusters as a case study.
- It provides a protocol using Fiji (ImageJ) and Matlab for defining regions, tracking particles, and analyzing their diffusion and intensity characteristics.
- This technique enables researchers to automate the analysis of particle dynamics, classify movement types, and evaluate the impact of environmental changes on particle behavior.
Evidence indicates an intimate connection between the neuroendocrine and the immune systems. A number of and studies have demonstrated growth hormone (GH) involvement in immune regulation. The GH receptor is expressed by several leukocyte subpopulations, and GH modulates immune cell proliferation and activity.
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- Chemokines are crucial in directing the movement of leukocytes during both normal and inflammatory immune responses by binding to G protein-coupled receptors.
- Advances in research over the past 25 years have revealed important details about how chemokines interact with receptors and their roles in various immune processes.
- Recent biophysical techniques have demonstrated that chemokine receptors can form complex structures, such as dimers and oligomers, highlighting the intricate networks in which they operate and suggesting new potential therapeutic targets.
Article Synopsis
- Current studies in cell motility aim to understand how the organization of chemokine receptors at the cell membrane affects cell behavior, particularly focusing on the chemokine receptor CXCR4 in T cells.
- Using advanced imaging techniques, researchers found that CXCR4 forms nanoclusters in resting T cells, which are influenced by the actin cytoskeleton, the CD4 co-receptor, and its ligand CXCL12.
- The study identified key structural residues in CXCR4 necessary for these nanoclusters, demonstrating that without proper clustering, even receptor dimerization can't effectively support signaling and cell functions in response to CXCL12.
During budding, lentiviral particles (LVP) incorporate cell membrane proteins in the viral envelope. We explored the possibility of harnessing this process to generate LVP-expressing membrane proteins of therapeutic interest and studied the potential of these tools to treat different pathologies. Fas-mediated apoptosis is central to the maintenance of T cell homeostasis and prevention of autoimmune processes.
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- Chemokines play key roles in various physiological and pathological processes by binding to receptors that activate signaling events.
- Chemokine receptors exist as dynamic dimers and oligomers on cell surfaces, influenced by receptor expression and ligand availability.
- New techniques, like resonance energy transfer, are being used to study the conformations and dynamics of these receptors in living cells for a better understanding of chemokine function.
Article Synopsis
- * Chemokine receptors are G protein-coupled proteins that transmit signals by binding to chemokines, and traditional studies often involve techniques that can alter their natural binding properties.
- * The review highlights various methods for attaching chemokine receptors to optical biosensors, discussing the pros and cons of each approach, and introduces a technique using viral particles to maintain the integrity of the receptors during analysis with surface plasmon resonance (SPR).
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation in joints, associated with synovial hyperplasia and with bone and cartilage destruction. Although the primacy of T cell-related events early in the disease continues to be debated, there is strong evidence that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. In addition, T cells are key components of the immune cell infiltrate detected in the joints of RA patients.
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- * Researchers examined the influence of vasoactive intestinal peptide (VIP) on Th17 cell differentiation, finding that VIP can modify the cells' pathogenic characteristics.
- * Results showed that Th17 cells from healthy donors had a nonpathogenic profile, while those from early RA patients displayed a more pathogenic profile; VIP was effective in reducing this pathogenicity and promoting a healthier Treg/Th17 balance.
The adaptive immune response requires interaction between T cells and APC to form a specialized structure termed the immune synapse (IS). Although the TCR is essential for IS organization, other factors such as chemokines participate in this process. In this study, we show that the chemokine CXCL12-mediated signaling contributes to correct IS organization and therefore influences T cell activation.
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