@article{10902/27268,
year = {2022},
url = {https://hdl.handle.net/10902/27268},
abstract = {In CD38-deficient ( <i><i>Cd38<sup>-/-</sup></i> )</i> mice intraperitoneal injection of pristane induces a lupus-like disease, which is milder than that induced in WT mice, showing significant differences in the inflammatory and autoimmune processes triggered by pristane. Extracellular vesicles (EV) are present in all body fluids. Shed by cells, their molecular make-up reflects that of their cell of origin and/or tissue pathological situation. The aim of this study was to analyze the protein composition, protein abundance, and functional clustering of EV released by peritoneal exudate cells (PECs) in the pristane experimental lupus model, to identify predictive or diagnostic biomarkers that might discriminate the autoimmune process in lupus from inflammatory reactions and/or normal physiological processes. In this study, thanks to an extensive proteomic analysis and powerful bioinformatics software, distinct EV subtypes were identified in the peritoneal exudates of pristane-treated mice: 1) small EV enriched in the tetraspanin CD63 and CD9, which are likely of exosomal origin; 2) small EV enriched in CD47 and CD9, which are also enriched in plasma-membrane, membrane-associated proteins, with an ectosomal origin; 3) small EV enriched in keratins, ECM proteins, complement/coagulation proteins, fibrin clot formation proteins, and endopetidase inhibitor proteins. This enrichment may have an inflammation-mediated mesothelial-to-mesenchymal transition origin, representing a protein corona on the surface of peritoneal exudate EV; 4) HDL-enriched lipoprotein particles. Quantitative proteomic analysis allowed us to identify an anti-inflammatory, Annexin A1-enriched pro-resolving, neutrophil protein signature, which was more prominent in EV from pristane-treated <i>Cd38<sup>-/-</sup></i> mice, and quantitative differences in the protein cargo of the ECM-enriched EV from <i>Cd38<sup>-/-</sup></i> vs WT mice. These differences are likely to be related with the distinct inflammatory outcome shown by <i>Cd38<sup>-/-</sup></i> vs WT mice in response to pristane treatment. Our results demonstrate the power of a hypothesis-free and data-driven approach to transform the heterogeneity of the peritoneal exudate EV from pristane-treated mice in valuable information about the relative proportion of different EV in a given sample and to identify potential protein markers specific for the different small EV subtypes, in particular those proteins defining EV involved in the resolution phase of chronic inflammation.},
organization = {Financial support: JS and MZ: Grant SAF-2017-89801-R (Proyecto del plan estatal, Ministerio de Ciencia e Innovación). RM: Grant: PID2020-119567RB-I00. The Proteomic Unit of the IPBLN-CSIC belongs to Proteo-Red-ISCIII (PRB2 and PRB3) and is supported by grants PT13/0001/011 and PT17/0019/0010 CSIC supported in part the article processing charges.},
publisher = {Frontiers Research Foundation},
publisher = {Frontiers in Immunology, 2022, 13, 1013236},
title = {Extracellular vesicles from pristane-treated CD38-deficient mice express an anti-inflammatory neutrophil protein signature, which reflects the mild lupus severity elicited in these mice},
author = {Carrillo-Rodríguez, Paula and Robles-Guirado, José-Ángel and Cruz-Palomares, Adrián and Palacios-Pedrero, Miguel Ángel and González-Paredes, Elena and Más-Ciurana, Alex and Franco-Herrera, Carolina and Ruiz-de-Castroviejo-Teba, Paloma A and Lario, Antonio and Longobardo, Victoria and Montosa-Hidalgo, Laura and Pérez-Sánchez-Cañete, María M and Corzo-Corbera, María-Mercedes and Redondo-Sánchez, Sandra and Jodar, Ana-Belén and Blanco, Francisco J and Zumaquero, Esther and Merino Pérez, Ramón and Sancho, Jaime and Zubiaur, Mercedes},
}