{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:16:28Z","timestamp":1782818188669,"version":"3.54.5"},"reference-count":78,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Carlos III Health Research Fund","doi-asserted-by":"publisher","award":["PI17\/01655"],"award-info":[{"award-number":["PI17\/01655"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Carlos III Health Research Fund","doi-asserted-by":"publisher","award":["RYC2021-032676-I"],"award-info":[{"award-number":["RYC2021-032676-I"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MCIN\/AEI\/10.13039\/501100011033","award":["PI17\/01655"],"award-info":[{"award-number":["PI17\/01655"]}]},{"name":"MCIN\/AEI\/10.13039\/501100011033","award":["RYC2021-032676-I"],"award-info":[{"award-number":["RYC2021-032676-I"]}]},{"name":"European Social Fund, ESF","award":["PI17\/01655"],"award-info":[{"award-number":["PI17\/01655"]}]},{"name":"European Social Fund, ESF","award":["RYC2021-032676-I"],"award-info":[{"award-number":["RYC2021-032676-I"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u201cproof-of-concept\u201d 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).<\/jats:p>","DOI":"10.3390\/ijms251910848","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T06:30:03Z","timestamp":1728455403000},"page":"10848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Signature Proteins in Small Extracellular Vesicles of Granulocytes and CD4+ T-Cell Subpopulations Identified by Comparative Proteomic Analysis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4540-8013","authenticated-orcid":false,"given":"Sara","family":"V\u00e1zquez-Mera","sequence":"first","affiliation":[{"name":"BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Migu\u00e9ns-Su\u00e1rez","sequence":"additional","affiliation":[{"name":"BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6303-0157","authenticated-orcid":false,"given":"Laura","family":"Martelo-Vidal","sequence":"additional","affiliation":[{"name":"BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Rivas-L\u00f3pez","sequence":"additional","affiliation":[{"name":"BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Uller","sequence":"additional","affiliation":[{"name":"Department of Experimental Medical Science, Lund University, 22362 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7615-3079","authenticated-orcid":false,"given":"Susana B.","family":"Bravo","sequence":"additional","affiliation":[{"name":"Proteomic Service, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3500-5915","authenticated-orcid":false,"given":"Vicente","family":"Dom\u00ednguez-Arca","sequence":"additional","affiliation":[{"name":"Biophysics and Interfaces Group, Applied Physics Department, Faculty of Physics, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 08035 Barcelona, Spain"},{"name":"Pneumology Service, Hospital Vall d\u2019Hebron Barcelona, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Gonz\u00e1lez-Barcala","sequence":"additional","affiliation":[{"name":"BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"},{"name":"Centro de Investigaci\u00f3n en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), 08035 Barcelona, Spain"},{"name":"Department of Respiratory Medicine, University Hospital Complex of Santiago de Compostela, 15706 Santiago de Compostela, Spain"},{"name":"Department of Medicine, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4647-1508","authenticated-orcid":false,"given":"Juan J.","family":"Nieto Fontarigo","sequence":"additional","affiliation":[{"name":"BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"},{"name":"Department 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Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Hazrati, A., Soudi, S., Malekpour, K., Mahmoudi, M., Rahimi, A., Hashemi, S.M., and Varma, R.S. (2022). Immune Cells-Derived Exosomes Function as a Double-Edged Sword: Role in Disease Progression and Their Therapeutic Applications. Biomark. Res., 10.","DOI":"10.1186\/s40364-022-00374-4"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"134970","DOI":"10.1016\/j.cej.2022.134970","article-title":"Synthesis, Bioactive Properties, and Biomedical Applications of Intrinsically Therapeutic Nanoparticles for Disease Treatment","volume":"435","author":"Nguyen","year":"2022","journal-title":"Chem. Eng. J."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wang, N., Wang, Q., Du, T., Gabriel, A.N.A., Wang, X., Sun, L., Li, X., Xu, K., Jiang, X., and Zhang, Y. (2020). The Potential Roles of Exosomes in Chronic Obstructive Pulmonary Disease. Front. Med., 7.","DOI":"10.3389\/fmed.2020.618506"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/all.15480","article-title":"Serum Exosome Inflamma-miRs Are Surrogate Biomarkers for Asthma Phenotype and Severity","volume":"78","author":"Arias","year":"2023","journal-title":"Allergy"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"103260","DOI":"10.1016\/j.autrev.2022.103260","article-title":"Exosomes as Biomarkers and Therapeutic Delivery for Autoimmune Diseases: Opportunities and Challenges","volume":"22","author":"Fang","year":"2023","journal-title":"Autoimmun. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"00658","DOI":"10.1183\/23120541.00658-2020","article-title":"Proteomics of Serum Extracellular Vesicles Identifies a Novel COPD Biomarker, Fibulin-3 from Elastic Fibres","volume":"7","author":"Koba","year":"2021","journal-title":"ERJ Open Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106773","DOI":"10.1016\/j.intimp.2020.106773","article-title":"Proteomic Analysis of Serum-Derived Extracellular Vesicles in Ankylosing Spondylitis Patients","volume":"87","author":"Huang","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9290","DOI":"10.1093\/nar\/gkx706","article-title":"A Comprehensive, Cell Specific microRNA Catalogue of Human Peripheral Blood","volume":"45","author":"Juzenas","year":"2017","journal-title":"Nucleic. Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/ni.2057","article-title":"Distinct microRNA Signatures in Human Lymphocyte Subsets and Enforcement of the Naive State in CD4+ T Cells by the microRNA miR-125b","volume":"12","author":"Rossi","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1002\/eji.201545787","article-title":"The Circulating microRNome Demonstrates Distinct Lymphocyte Subset-Dependent Signatures","volume":"46","author":"Torri","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1016\/j.jaci.2023.12.030","article-title":"Galectin-10 in Serum Extracellular Vesicles Reflects Asthma Pathophysiology","volume":"153","author":"Yoshimura","year":"2024","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_13","first-page":"325","article-title":"Surface Proteome of Plasma Extracellular Vesicles as Biomarkers for Pneumonia and Acute Exacerbation of Chronic Obstructive Pulmonary Disease","volume":"221","author":"Jung","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zebrowska, A., Jelonek, K., Mondal, S., Gawin, M., Mrowiec, K., Wid\u0142ak, P., Whiteside, T., and Pietrowska, M. (2022). Proteomic and Metabolomic Profiles of T Cell-Derived Exosomes Isolated from Human Plasma. Cells, 11.","DOI":"10.3390\/cells11121965"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1002\/eji.201847655","article-title":"Proteomic Analysis of Human T Cell-Derived Exosomes Reveals Differential RAS\/MAPK Signaling","volume":"48","author":"Mor","year":"2018","journal-title":"Eur. J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1189\/jlb.1212619","article-title":"Proteome Profiling of Human Neutrophil Granule Subsets, Secretory Vesicles, and Cell Membrane: Correlation with Transcriptome Profiling of Neutrophil Precursors","volume":"94","author":"Heegaard","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14086","DOI":"10.1111\/jcmm.16020","article-title":"T Cell-Derived Exosomes Induced Macrophage Inflammatory Protein-1\u03b1\/\u03b2 Drive the Trafficking of CD8+ T Cells in Oral Lichen Planus","volume":"24","author":"Yang","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"117773","DOI":"10.1016\/j.cca.2024.117773","article-title":"Exosomal miRNAs from Neutrophils Act as Accurate Biomarkers for Gastric Cancer Diagnosis","volume":"554","author":"Yu","year":"2024","journal-title":"Clin. Chim. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1016\/j.jaci.2014.11.026","article-title":"Exosome Secretion by Eosinophils: A Possible Role in Asthma Pathogenesis","volume":"135","author":"Mazzeo","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"V\u00e1zquez-Mera, S., Martelo-Vidal, L., Migu\u00e9ns-Su\u00e1rez, P., Bravo, S.B., Saavedra-Nieves, P., Arias, P., Ferreiro-Posse, A., V\u00e1zquez-Lago, J., Salgado, F.J., and Gonz\u00e1lez-Barcala, F.J. (2024). Exploring CD26\u00a0\u2212\/lo Subpopulations of Lymphocytes in Asthma Phenotype and Severity: A Novel CD4\u00a0+ T Cell Subset Expressing Archetypical Granulocyte Proteins. Allergy, 1\u201317.","DOI":"10.1111\/all.16327"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jaci.2016.05.011","article-title":"Inflammatory Mechanisms in Patients with Chronic Obstructive Pulmonary Disease","volume":"138","author":"Barnes","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.jaip.2022.11.025","article-title":"Association Between Blood Eosinophils and Neutrophils With Clinical Features in Adult-Onset Asthma","volume":"11","author":"Flinkman","year":"2023","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_23","first-page":"e13423","article-title":"Blood Eosinophils Could Be Useful as a Biomarker in Chronic Obstructive Pulmonary Disease Exacerbations","volume":"73","author":"Carreira","year":"2019","journal-title":"Int. J. Clin. Pract."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ejim.2018.02.034","article-title":"Association between Blood Eosinophil Count with Asthma Hospital Readmissions","volume":"53","author":"Carreira","year":"2018","journal-title":"Eur. J. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2102288","DOI":"10.1183\/13993003.02288-2021","article-title":"T2-High Asthma Phenotypes across Lifespan","volume":"60","author":"Maison","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1111\/all.15056","article-title":"From DREAM to REALITI-A and beyond: Mepolizumab for the Treatment of Eosinophil-Driven Diseases","volume":"77","author":"Pavord","year":"2022","journal-title":"Allergy"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1189\/jlb.3AB0516-233RR","article-title":"Exosomes from Eosinophils Autoregulate and Promote Eosinophil Functions","volume":"101","author":"Sastre","year":"2017","journal-title":"J. Leukoc. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6813","DOI":"10.1096\/fj.201802090RR","article-title":"Neutrophil Exosomes Enhance the Skin Autoinflammation in Generalized Pustular Psoriasis via Activating Keratinocytes","volume":"33","author":"Shao","year":"2019","journal-title":"FASEB J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e00596-20","DOI":"10.1128\/mBio.00596-20","article-title":"Human Neutrophils Produce Antifungal Extracellular Vesicles against Aspergillus Fumigatus","volume":"11","author":"Shopova","year":"2020","journal-title":"mBio"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kruzel, M.L., Zimecki, M., and Actor, J.K. (2017). Lactoferrin in a Context of Inflammation-Induced Pathology. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01438"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Jaberi, S.A., Cohen, A., D\u2019Souza, C., Abdulrazzaq, Y.M., Ojha, S., Bastaki, S., and Adeghate, E.A. (2021). Lipocalin-2: Structure, Function, Distribution and Role in Metabolic Disorders. Biomed. Pharmacother., 142.","DOI":"10.1016\/j.biopha.2021.112002"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1189\/jlb.1204697","article-title":"Myeloperoxidase: Friend and Foe","volume":"77","author":"Klebanoff","year":"2005","journal-title":"J. Leukoc. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"189","DOI":"10.2147\/COPD.S235903","article-title":"Serum Levels of Autoantibodies Against Extracellular Antigens and Neutrophil Granule Proteins Increase in Patients with COPD Compared to Non-COPD Smokers","volume":"15","author":"Ma","year":"2020","journal-title":"Int. J. Chron. Obstruct. Pulmon. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e3939","DOI":"10.1093\/cid\/ciaa1843","article-title":"Biomarkers to Distinguish Bacterial From Viral Pediatric Clinical Pneumonia in a Malaria-Endemic Setting","volume":"73","author":"Gillette","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jinf.2021.05.039","article-title":"Distinguishing Septic Shock from Non-Septic Shock in Postsurgical Patients Using Gene Expression","volume":"83","author":"Liu","year":"2021","journal-title":"J. Infect."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e23207","DOI":"10.1097\/MD.0000000000023207","article-title":"Screening of Potential Biomarkers for Distinguishing between Latent and Active Tuberculosis in Children Using Bioinformatics Analysis","volume":"100","author":"Shao","year":"2021","journal-title":"Medicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.arcmed.2012.08.008","article-title":"Immune Response to Seasonal Influenza A Virus Infection: A Proteomic Approach","volume":"43","author":"Teran","year":"2012","journal-title":"Arch. Med. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1111\/jcmm.16275","article-title":"Identification of Key Candidate Biomarkers for Severe Influenza Infection by Integrated Bioinformatical Analysis and Initial Clinical Validation","volume":"25","author":"Liu","year":"2021","journal-title":"J. Cell Mol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e144455","DOI":"10.1172\/jci.insight.144455","article-title":"An Immune-Based Biomarker Signature Is Associated with Mortality in COVID-19 Patients","volume":"6","author":"Abers","year":"2021","journal-title":"JCI Insight"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.molimm.2017.09.021","article-title":"Identification of Potential Transcriptomic Markers in Developing Asthma: An Integrative Analysis of Gene Expression Profiles","volume":"92","author":"Fang","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Delgado, L., Vega-Rioja, A., Ventura, I., Chamorro, C., Aroca, R., Prados, M., Bobadilla, P., Rodr\u00edguez, D., Palacios, R., and Monteseir\u00edn, J. (2015). Allergens Induce the Release of Lactoferrin by Neutrophils from Asthmatic Patients. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141278"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nie, X., Wei, J., Hao, Y., Tao, J., Li, Y., Liu, M., Xu, B., and Li, B. (2019). Consistent Biomarkers and Related Pathogenesis Underlying Asthma Revealed by Systems Biology Approach. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20164037"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1139\/o06-058","article-title":"Regulation of Physiological and Pathological Th1 and Th2 Responses by Lactoferrin","volume":"84","author":"Fischer","year":"2006","journal-title":"Biochem. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1365-2567.2006.02417.x","article-title":"Lactoferrin Decreases Pollen Antigen-Induced Allergic Airway Inflammation in a Murine Model of Asthma","volume":"119","author":"Kruzel","year":"2006","journal-title":"Immunology"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Lin, C.-C., Chuang, K.-C., Chen, S.-W., Chao, Y.-H., Yen, C.-C., Yang, S.-H., Chen, W., Chang, K.-H., Chang, Y.-K., and Chen, C.-M. (2022). Lactoferrin Ameliorates Ovalbumin-Induced Asthma in Mice through Reducing Dendritic-Cell-Derived Th2 Cell Responses. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214185"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Palmer, C., Diehn, M., Alizadeh, A.A., and Brown, P.O. (2006). Cell-Type Specific Gene Expression Profiles of Leukocytes in Human Peripheral Blood. BMC Genom., 7.","DOI":"10.1186\/1471-2164-7-115"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1073\/pnas.252784499","article-title":"Individuality and Variation in Gene Expression Patterns in Human Blood","volume":"100","author":"Whitney","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1111\/cas.12534","article-title":"Exosome Proteomics Reveals Transcriptional Regulator Proteins with Potential to Mediate Downstream Pathways","volume":"105","author":"Ung","year":"2014","journal-title":"Cancer Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wahlgren, J., Karlson, T.D.L., Glader, P., Telemo, E., and Valadi, H. (2012). Activated Human T Cells Secrete Exosomes That Participate in IL-2 Mediated Immune Response Signaling. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049723"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"de Candia, P., Torri, A., Pagani, M., and Abrignani, S. (2014). Serum microRNAs as Biomarkers of Human Lymphocyte Activation in Health and Disease. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00043"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1111\/all.13760","article-title":"Inflammatory Endotypes in COPD","volume":"74","author":"Barnes","year":"2019","journal-title":"Allergy"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s12016-018-8712-1","article-title":"Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease","volume":"56","author":"Kuruvilla","year":"2019","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Zhu, X., and Zhu, J. (2020). CD4 T Helper Cell Subsets and Related Human Immunological Disorders. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218011"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/ni.3693","article-title":"Social Network Architecture of Human Immune Cells Unveiled by Quantitative Proteomics","volume":"18","author":"Rieckmann","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Subbannayya, Y., Haug, M., Pinto, S.M., Mohanty, V., Me\u00e5s, H.Z., Flo, T.H., Prasad, T.S.K., and Kandasamy, R.K. (2020). The Proteomic Landscape of Resting and Activated CD4+ T Cells Reveal Insights into Cell Differentiation and Function. Int. J. Mol. Sci., 22.","DOI":"10.1101\/2020.11.17.385096"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.antiviral.2016.07.013","article-title":"Exosomes Contribute to the Transmission of Anti-HIV Activity from TLR3-Activated Brain Microvascular Endothelial Cells to Macrophages","volume":"134","author":"Sun","year":"2016","journal-title":"Antiviral. Res"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Xiao, L., Zhan, F., and Lin, S. (2022). Clinical Values of the Identified Hub Genes in Systemic Lupus Erythematosus. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.844025"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Li, L., Ni, Y.A., Song, Z., Yi, Z., and Wang, F. (2021). Identification of Pathogenic Genes and Transcription Factors in Respiratory Syncytial Virus. BMC Pediatr., 21.","DOI":"10.1186\/s12887-020-02480-4"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/s41579-018-0020-5","article-title":"ISG15 in Antiviral Immunity and Beyond","volume":"16","author":"Perng","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.molcel.2017.10.003","article-title":"Extracellular ISG15 Signals Cytokine Secretion through the LFA-1 Integrin Receptor","volume":"68","author":"Swaim","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1128\/JVI.02110-14","article-title":"Novel Mode of ISG15-Mediated Protection against Influenza A Virus and Sendai Virus in Mice","volume":"89","author":"Morales","year":"2015","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"916778","DOI":"10.3389\/fimmu.2022.916778","article-title":"Th2A Cells: The Pathogenic Players in Allergic Diseases","volume":"13","author":"Huang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ebiom.2018.05.037","article-title":"Leptin\/Osteopontin Axis Regulated Type 2T Helper Cell Response in Allergic Rhinitis with Obesity","volume":"32","author":"Zeng","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5884","DOI":"10.2174\/0929867328666210217153609","article-title":"An Overview of the A4\u03b21 Integrin and the Potential Therapeutic Role of Its Antagonists","volume":"28","author":"Ferreira","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.humimm.2009.09.360","article-title":"Co-Engagement of Alpha(4)Beta(1) Integrin (VLA-4) and CD4 or CD8 Is Necessary to Induce Maximal Erk1\/2 Phosphorylation and Cytokine Production in Human T Cells","volume":"71","author":"Kim","year":"2010","journal-title":"Hum. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Mercurio, L., Morelli, M., Scarponi, C., Scaglione, G.L., Pallotta, S., Avitabile, D., Albanesi, C., and Madonna, S. (2021). Enhanced NAMPT-Mediated NAD Salvage Pathway Contributes to Psoriasis Pathogenesis by Amplifying Epithelial Auto-Inflammatory Circuits. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136860"},{"key":"ref_67","first-page":"251","article-title":"Gene Expression Profiling of Peripheral Blood Mononuclear Leukocytes from Psoriasis Patients Identifies New Immune Regulatory Molecules","volume":"15","author":"Koczan","year":"2005","journal-title":"Eur. J. Dermatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1177\/147323000903700601","article-title":"Visfatin: A Potential Therapeutic Target for Rheumatoid Arthritis","volume":"37","author":"Bao","year":"2009","journal-title":"J. Int. Med. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s00109-020-01892-0","article-title":"Neutralization of Extracellular NAMPT (Nicotinamide Phosphoribosyltransferase) Ameliorates Experimental Murine Colitis","volume":"98","author":"Colombo","year":"2020","journal-title":"J. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1560809","DOI":"10.1080\/20013078.2018.1560809","article-title":"Comparison of Small Extracellular Vesicles Isolated from Plasma by Ultracentrifugation or Size-Exclusion Chromatography: Yield, Purity and Functional Potential","volume":"8","author":"Takov","year":"2019","journal-title":"J. Extracell. Vesicles"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"110277","DOI":"10.1016\/j.celrep.2021.110277","article-title":"Tissue Differences in the Exosomal\/Small Extracellular Vesicle Proteome and Their Potential as Indicators of Altered Tissue Metabolism","volume":"38","author":"Brandao","year":"2022","journal-title":"Cell Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"6391264","DOI":"10.1155\/2016\/6391264","article-title":"Phenotyping of Leukocytes and Leukocyte-Derived Extracellular Vesicles","volume":"2016","author":"Pugholm","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1378\/chest.14-2457","article-title":"Biomarker Profiles in Asthma With High vs Low Airway Reversibility and Poor Disease Control","volume":"148","author":"Busse","year":"2015","journal-title":"Chest"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"113","DOI":"10.18176\/jiaci.0224","article-title":"Expansion of a CD26low Effector TH Subset and Reduction in Circulating Levels of sCD26 in Stable Allergic Asthma in Adults","volume":"28","author":"Cruz","year":"2018","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_75","first-page":"3.22.1","article-title":"Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids","volume":"30","author":"Amigorena","year":"2006","journal-title":"Curr. Protoc. Cell Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-1-0716-1178-4_7","article-title":"SWATH-MS Protocols in Human Diseases","volume":"2259","author":"Serna","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Pe\u00f1as-Mart\u00ednez, J., Barrachina, M.N., Cuenca-Zamora, E.J., Luengo-Gil, G., Bravo, S.B., Caparr\u00f3s-P\u00e9rez, E., Teruel-Montoya, R., Eliseo-Blanco, J., Vicente, V., and Garc\u00eda, \u00c1. (2021). Qualitative and Quantitative Comparison of Plasma Exosomes from Neonates and Adults. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041926"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1021\/ac950914h","article-title":"Mass Spectrometric Sequencing of Proteins Silver-Stained Polyacrylamide Gels","volume":"68","author":"Shevchenko","year":"1996","journal-title":"Anal. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10848\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:09:50Z","timestamp":1760112590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/19\/10848"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,9]]},"references-count":78,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["ijms251910848"],"URL":"https:\/\/doi.org\/10.3390\/ijms251910848","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,9]]}}}