Suppressor of cytokine signaling-3 expression and its regulation in relation to inflammation in Chronic Obstructive Pulmonary Disease
BackgroundThe family of Suppressor of Cytokine Signaling (SOCS) acts as a controller of the duration and intensity of cytokine function by negatively regulating the JAK-STAT signaling pathway. SOCS’ role in inflammatory diseases in animal models is well demonstrated. However, its role in the develop...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1320077/full |
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| author | Mariaenrica Tinè Elisabetta Balestro Sara Carpi Sara Carpi Tommaso Neri Davide Biondini Davide Biondini Maria Conti Alvise Casara Nicol Bernardinello Elisabetta Cocconcelli Graziella Turato Simonetta Baraldo Alessandro Celi Paolo Spagnolo Manuel G. Cosio Manuel G. Cosio Marina Saetta Erica Bazzan |
| author_facet | Mariaenrica Tinè Elisabetta Balestro Sara Carpi Sara Carpi Tommaso Neri Davide Biondini Davide Biondini Maria Conti Alvise Casara Nicol Bernardinello Elisabetta Cocconcelli Graziella Turato Simonetta Baraldo Alessandro Celi Paolo Spagnolo Manuel G. Cosio Manuel G. Cosio Marina Saetta Erica Bazzan |
| author_sort | Mariaenrica Tinè |
| collection | DOAJ |
| description | BackgroundThe family of Suppressor of Cytokine Signaling (SOCS) acts as a controller of the duration and intensity of cytokine function by negatively regulating the JAK-STAT signaling pathway. SOCS’ role in inflammatory diseases in animal models is well demonstrated. However, its role in the development of human disease is still under investigation. SOCS3 plays an important role in tumor development where its downregulation has been implicated in the pathogenesis of various solid tumors such as triple-negative breast cancer.AimThe aim of this work was to study (1) the expression of SOCS3 in smokers’ lungs and its relation to the degree of inflammation and (2) SOCS3 regulation by microRNA (miRNA) in alveolar-macrophage (AM)-derived extracellular vesicles (EVs) in bronchoalveolar lavage (BAL).MethodsGroup A: 35 smokers’ [19 with COPD (SC) and 16 without COPD (S)] and 9 nonsmokers (NS); SOCS3, TNFα in AM, and CD8+ T cells were quantified by immunohistochemistry, in lung tissue. Group B: additional 9 SC, 11 S, and 5 NS; AM-EVs expressing SOCS3 (CD14+SOCS3+) and SOCS3 suppressors miRNA-19a-3p and 221-3p in EVs were quantified by flow cytometry and PCR, in BAL.ResultsThe percentage of SOCS3+ AM was higher in SC [68 (6.6–99)%] and S [48 (8–100)%] than in NS [9.6 (1.9–61)%; p = 0.002; p = 0.03] and correlated with % of TNFα+AM (r = 0.48; p = 0.0009) and CD8+ T cells (r = 0.44; p = 0.0029). In BAL, the CD14+SOCS3+ EVs/μL were increased in SC [33 (21–74)] compared to S [16 (8–37); p = 0.03] and NS [9 (7–21); p = 0.003]. Conversely, miRNA-19a-3p and miRNA-221-3p expression were increased in S when compared to SC [19 (2–53) vs. 3 (0.6–8); p = 0.03 and 3 (0.005–9.6) vs. 0.2 (0.08–0.7); p = 0.05].ConclusionsThe suppressor function of SOCS3 in COPD seems to be overridden by other factors and does not follow the animal-model paradigm. Expression of SOCS3 in BAL macrophage-derived EVs might be useful to assess the degree of inflammation and possible progression of COPD. Downregulation of SOCS3, by miRNA, in smokers without COPD might contribute to the risk of developing cancer in these patients. |
| first_indexed | 2024-04-25T00:46:32Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-25T00:46:32Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-95720d0107b34876be93c27775dc8c752024-03-12T04:35:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13200771320077Suppressor of cytokine signaling-3 expression and its regulation in relation to inflammation in Chronic Obstructive Pulmonary DiseaseMariaenrica Tinè0Elisabetta Balestro1Sara Carpi2Sara Carpi3Tommaso Neri4Davide Biondini5Davide Biondini6Maria Conti7Alvise Casara8Nicol Bernardinello9Elisabetta Cocconcelli10Graziella Turato11Simonetta Baraldo12Alessandro Celi13Paolo Spagnolo14Manuel G. Cosio15Manuel G. Cosio16Marina Saetta17Erica Bazzan18Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, ItalyDepartment of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, ItalyDepartment of Health Sciences, University ‘Magna Græcia’ of Catanzaro, Catanzaro, ItalyNational Enterprise for NanoScience and NanoTechnology (NEST), Istituto Nanoscienze-Centro Nazionale Ricerche (CNR) and Scuola Normale Superiore, Pisa, ItalyCentro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell’Area Critica, Università degli Studi di Pisa, Pisa, ItalyDepartment of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, ItalyDepartment of Medicine, University of Padova, Padova, ItalyDepartment of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, ItalyDepartment of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, ItalyDepartment of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, ItalyDepartment of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, ItalyDepartment of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, ItalyDepartment of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, ItalyCentro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell’Area Critica, Università degli Studi di Pisa, Pisa, ItalyDepartment of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, ItalyDepartment of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, ItalyMeakins-Christie Laboratories, Respiratory Division, McGill University, Montreal, QC, CanadaDepartment of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, ItalyDepartment of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padova, ItalyBackgroundThe family of Suppressor of Cytokine Signaling (SOCS) acts as a controller of the duration and intensity of cytokine function by negatively regulating the JAK-STAT signaling pathway. SOCS’ role in inflammatory diseases in animal models is well demonstrated. However, its role in the development of human disease is still under investigation. SOCS3 plays an important role in tumor development where its downregulation has been implicated in the pathogenesis of various solid tumors such as triple-negative breast cancer.AimThe aim of this work was to study (1) the expression of SOCS3 in smokers’ lungs and its relation to the degree of inflammation and (2) SOCS3 regulation by microRNA (miRNA) in alveolar-macrophage (AM)-derived extracellular vesicles (EVs) in bronchoalveolar lavage (BAL).MethodsGroup A: 35 smokers’ [19 with COPD (SC) and 16 without COPD (S)] and 9 nonsmokers (NS); SOCS3, TNFα in AM, and CD8+ T cells were quantified by immunohistochemistry, in lung tissue. Group B: additional 9 SC, 11 S, and 5 NS; AM-EVs expressing SOCS3 (CD14+SOCS3+) and SOCS3 suppressors miRNA-19a-3p and 221-3p in EVs were quantified by flow cytometry and PCR, in BAL.ResultsThe percentage of SOCS3+ AM was higher in SC [68 (6.6–99)%] and S [48 (8–100)%] than in NS [9.6 (1.9–61)%; p = 0.002; p = 0.03] and correlated with % of TNFα+AM (r = 0.48; p = 0.0009) and CD8+ T cells (r = 0.44; p = 0.0029). In BAL, the CD14+SOCS3+ EVs/μL were increased in SC [33 (21–74)] compared to S [16 (8–37); p = 0.03] and NS [9 (7–21); p = 0.003]. Conversely, miRNA-19a-3p and miRNA-221-3p expression were increased in S when compared to SC [19 (2–53) vs. 3 (0.6–8); p = 0.03 and 3 (0.005–9.6) vs. 0.2 (0.08–0.7); p = 0.05].ConclusionsThe suppressor function of SOCS3 in COPD seems to be overridden by other factors and does not follow the animal-model paradigm. Expression of SOCS3 in BAL macrophage-derived EVs might be useful to assess the degree of inflammation and possible progression of COPD. Downregulation of SOCS3, by miRNA, in smokers without COPD might contribute to the risk of developing cancer in these patients.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1320077/fullsocs3extracellular vesiclesCOPDmiRNAhuman BALalveolar macrophages |
| spellingShingle | Mariaenrica Tinè Elisabetta Balestro Sara Carpi Sara Carpi Tommaso Neri Davide Biondini Davide Biondini Maria Conti Alvise Casara Nicol Bernardinello Elisabetta Cocconcelli Graziella Turato Simonetta Baraldo Alessandro Celi Paolo Spagnolo Manuel G. Cosio Manuel G. Cosio Marina Saetta Erica Bazzan Suppressor of cytokine signaling-3 expression and its regulation in relation to inflammation in Chronic Obstructive Pulmonary Disease Frontiers in Immunology socs3 extracellular vesicles COPD miRNA human BAL alveolar macrophages |
| title | Suppressor of cytokine signaling-3 expression and its regulation in relation to inflammation in Chronic Obstructive Pulmonary Disease |
| title_full | Suppressor of cytokine signaling-3 expression and its regulation in relation to inflammation in Chronic Obstructive Pulmonary Disease |
| title_fullStr | Suppressor of cytokine signaling-3 expression and its regulation in relation to inflammation in Chronic Obstructive Pulmonary Disease |
| title_full_unstemmed | Suppressor of cytokine signaling-3 expression and its regulation in relation to inflammation in Chronic Obstructive Pulmonary Disease |
| title_short | Suppressor of cytokine signaling-3 expression and its regulation in relation to inflammation in Chronic Obstructive Pulmonary Disease |
| title_sort | suppressor of cytokine signaling 3 expression and its regulation in relation to inflammation in chronic obstructive pulmonary disease |
| topic | socs3 extracellular vesicles COPD miRNA human BAL alveolar macrophages |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1320077/full |
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