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oai:recercat.cat:11351/122402025-10-24T10:29:17Zcom_2072_378070com_2072_378040col_2072_378092

Signature Proteins in Small Extracellular Vesicles of Granulocytes and CD4+ T-Cell Subpopulations Identified by Comparative Proteomic Analysis Vázquez-Mera, Sara Miguéns, Pablo MARTELO VIDAL, LAURA Rivas-López, Sara Uller, Lena Bravo Lopez, Susana Belén Muñoz, Xavier Institut Català de la Salut [Vázquez-Mera S, Miguéns-Suárez P, Martelo-Vidal L, Rivas-López S] BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain. Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. [Uller L] Department of Experimental Medical Science, Lund University, Lund, Sweden. [Bravo SB] Proteomic Service, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain. [Muñoz X] Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain. Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Marcadors bioquímics Proteòmica Cèl·lules T ANATOMY::Cells::Cellular Structures::Extracellular Space::Extracellular Vesicles CHEMICALS AND DRUGS::Biological Factors::Biomarkers DISCIPLINES AND OCCUPATIONS::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Proteomics ANATOMY::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes::CD4-Positive T-Lymphocytes ANATOMÍA::células::estructuras celulares::espacio extracelular::vesículas extracelulares COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores DISCIPLINAS Y OCUPACIONES::disciplinas de las ciencias naturales::disciplinas de las ciencias biológicas::bioquímica::proteómica ANATOMÍA::células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T::linfocitos T CD4-positivos Immune cells; Inflammatory diseases; Proteomics Células inmunes; Enfermedades inflamatorias; Proteómica Cèl·lules immunes; Malalties inflamatòries; Proteòmica Several studies have described the proteomic profile of different immune cell types, but only a few have also analysed the content of their delivered small extracellular vesicles (sEVs). The aim of the present study was to compare the protein signature of sEVs delivered from granulocytes (i.e., neutrophils and eosinophils) and CD4+ T cells (i.e., TH1, TH2, and TH17) to identify potential biomarkers of the inflammatory profile in chronic inflammatory diseases. Qualitative (DDA) and quantitative (DIA-SWATH) analyses of in vitro-produced sEVs revealed proteome variations depending on the cell source. The main differences were found between granulocyte- and TH cell-derived sEVs, with a higher abundance of antimicrobial proteins (e.g., LCN2, LTF, MPO) in granulocyte-derived sEVs and an enrichment of ribosomal proteins (RPL and RPS proteins) in TH-derived sEVs. Additionally, we found differentially abundant proteins between neutrophil and eosinophil sEVs (e.g., ILF2, LTF, LCN2) and between sEVs from different TH subsets (e.g., ISG15, ITGA4, ITGB2, or NAMPT). A “proof-of-concept” assay was also performed, with TH2 biomarkers ITGA4 and ITGB2 displaying a differential abundance in sEVs from T2high and T2low asthma patients. Thus, our findings highlight the potential use of these sEVs as a source of biomarkers for diseases where the different immune cell subsets studied participate, particularly chronic inflammatory pathologies such as asthma or chronic obstructive pulmonary disease (COPD). This work was funded by the Carlos III Health Research Fund (PI17/01655; miRNAs and exosome proteome in patients with asthma; microProtExAs). The publication is part of the grant RYC2021-032676-I financed by MCIN/AEI/10.13039/501100011033 and by the European Union’s NextGeneration EU/PRTR. SV-M and PM-S are recipients of a Xunta de Galicia PhD Fellowship (co-financed by the European Social Fund, ESF). 2024-11-20T08:47:41Z 2024-11-20T08:47:41Z 2024-10 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Vázquez-Mera S, Miguéns-Suárez P, Martelo-Vidal L, Rivas-López S, Uller L, Bravo SB, et al. Signature Proteins in Small Extracellular Vesicles of Granulocytes and CD4+ T-Cell Subpopulations Identified by Comparative Proteomic Analysis. Int J Mol Sci. 2024 Oct;25(19):10848. 1422-0067 https://hdl.handle.net/11351/12240 10.3390/ijms251910848 39409176 001334086900001 http://hdl.handle.net/11351/12240 eng International Journal of Molecular Sciences;25(19) https://doi.org/10.3390/ijms251910848 info:eu-repo/grantAgreement/ES/PE2017-2020/PI17%2F01655 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf MDPI Scientia