CD1 isoforms are MHC class I-like molecules that present lipid-antigens to T cells and have been associated with a variety of immune responses. The lipid repertoire bound and presented by the four CD1 isoforms may be influenced by factors such as the cellular lipidome, subcellular microenvironment, and the properties of the binding pocket. In this study, by shotgun mass spectrometry, we performed a comprehensive lipidomic analysis of soluble CD1 molecules. We identified 1040 lipids, of which 293 were present in all isoforms. Comparative analysis revealed that the isoforms bind almost any cellular lipid.CD1a and CD1c closely mirrored the cellular lipidome, while CD1b and CD1d showed a preference for sphingolipids. Each CD1 isoform was found to have unique lipid species, suggesting some distinct roles in lipid presentation and immune responses. These findings contribute to our understanding of the role of CD1 system in immunity and could have implications for the development of lipid-based therapeutics.
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http://dx.doi.org/10.3389/fimmu.2024.1462209 | DOI Listing |
Bioorg Med Chem
January 2025
Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, Via A. Moro 2, 53100 Siena, Italy.
The imidazo[1,5-a]quinoline scaffold of central benzodiazepine receptor (CBR) ligands was used as the pharmacophore in the design of bivalent ligands bearing spacers showing variable length and different physicochemical features. The newly designed compounds were synthesized along with the corresponding reference monovalent compounds bearing the corresponding spacers terminated with a tert-butoxycarbonyl group. The novel compounds were tested in binding assays with different CBR preparations such as the cerebral cortex from male CD-1 albino mice or the human recombinant α1β3γ2 and α2β3γ2 γ-aminobutyric acid type A receptors (GABARs) stably expressed in mouse L(tk-) cells.
View Article and Find Full Text PDFInt J Mol Sci
October 2024
Istituto Superiore di Sanità, National Centre for Drug Research and Evaluation, Viale Regina Elena 299, 00161 Rome, Italy.
Free fatty acid receptor 1 (FFAR1) has emerged as the most targeted isoform of the free fatty acid receptors because of its involvement in the modulation of energy balance and its potential role in the control of inflammatory and pain conditions. Quercetin-3-oleate (AV2), recognized as a new FFAR1 partial agonist, was investigated for its ability to modulate inflammation and nociception. Human immortal neuroblastoma SH and the murine macrophagic RAW 264.
View Article and Find Full Text PDFPathogens
October 2024
Unidad de Investigación UNAM-INC, División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México-Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City 14080, Mexico.
L-arginine metabolism through arginases and inducible nitric oxide synthase (NOS2) constitutes a fundamental axis for the resolution or progression of Chagas disease. Infection with can cause a wide spectrum of disease, ranging from acute forms contained by the host immune response to chronic ones, such as the chronic chagasic cardiomyopathy. Here, we analyzed, in an in vitro model, the ability of two isolates, with different degrees of virulence, to regulate the metabolism of L-arginine through arginase 1 (Arg-1) and NOS2 in macrophages and through arginase 2 (Arg-2) and NOS2 in cardiomyocytes.
View Article and Find Full Text PDFFront Immunol
September 2024
Immunocore Ltd, Experimental Immunology, Abingdon, United Kingdom.
CD1 isoforms are MHC class I-like molecules that present lipid-antigens to T cells and have been associated with a variety of immune responses. The lipid repertoire bound and presented by the four CD1 isoforms may be influenced by factors such as the cellular lipidome, subcellular microenvironment, and the properties of the binding pocket. In this study, by shotgun mass spectrometry, we performed a comprehensive lipidomic analysis of soluble CD1 molecules.
View Article and Find Full Text PDFSci Rep
June 2024
Department of Pharmacology, College of Medicine, University of Arizona, Box 245050, LSN563, 1501 N. Campbell Ave., Tucson, AZ, 85724, USA.
Opioids are the gold standard for the treatment of chronic pain but are limited by adverse side effects. In our earlier work, we showed that Heat shock protein 90 (Hsp90) has a crucial role in regulating opioid signaling in spinal cord; Hsp90 inhibition in spinal cord enhances opioid anti-nociception. Building on these findings, we injected the non-selective Hsp90 inhibitor KU-32 by the intrathecal route into male and female CD-1 mice, showing that morphine anti-nociceptive potency was boosted by 1.
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