{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:39:11Z","timestamp":1792471151253,"version":"4.5.0"},"reference-count":125,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T00:00:00Z","timestamp":1640822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cytokines are well known to play a central role in chronic rhinosinusitis with nasal polyps (CRSwNP), particularly in maintenance of the inflammatory response and the recruitment of eosinophils. The pathophysiological concepts concerning the involvement of inflammatory cytokines in CRSwNP have gradually evolved. Although the Th2 cytokines environment associated with an eosinophilic infiltration has retained a central role in the genesis of polyps, the role of other cytokine subpopulations has also and more recently been detailed, leading to a specific and complex signature in CRSwNP. The purpose of this review is to summarize the current state of knowledge about the cytokine signature in CRSwNP, the role of cytokines in the pathogenesis of this disease and in the intercellular dialog between epithelial cells, fibroblasts and inflammatory cells. Knowledge of this precise cytokine signature in CRSwNP is fundamental in the perspective of potential targeting biotherapies.<\/jats:p>","DOI":"10.3390\/ijms23010417","type":"journal-article","created":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T23:29:07Z","timestamp":1640906947000},"page":"417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Cytokine Signature and Involvement in Chronic Rhinosinusitis with Nasal Polyps"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5574-8559","authenticated-orcid":false,"given":"Florent","family":"Carsuzaa","sequence":"first","affiliation":[{"name":"Laboratoire Inflammation Tissus Epith\u00e9liaux et Cytokines (LITEC), Universit\u00e9 de Poitiers, 86000 Poitiers, France"},{"name":"Oto-Rhino-Laryngologie et Chirurgie Cervico-Maxillo-Faciale, Centre Hospitalier Universitaire de Poitiers, 86021 Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5193-5776","authenticated-orcid":false,"given":"\u00c9milie","family":"B\u00e9quignon","sequence":"additional","affiliation":[{"name":"Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, H\u00f4pital Henri Mondor et Centre Hospitalier Intercommunal de Cr\u00e9teil, 94010 Cr\u00e9teil, France"},{"name":"INSERM U955, \u00c9quipe 13, Centre Henri Mondor de Recherche Biom\u00e9dicale, 94000 Cr\u00e9teil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Dufour","sequence":"additional","affiliation":[{"name":"Laboratoire Inflammation Tissus Epith\u00e9liaux et Cytokines (LITEC), Universit\u00e9 de Poitiers, 86000 Poitiers, France"},{"name":"Oto-Rhino-Laryngologie et Chirurgie Cervico-Maxillo-Faciale, Centre Hospitalier Universitaire de Poitiers, 86021 Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"de Bonnecaze","sequence":"additional","affiliation":[{"name":"Oto-Rhino-Laryngologie et Chirurgie Cervico-Faciale, Centre Hospitalier Universitaire de Toulouse, 31400 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Claude","family":"Lecron","sequence":"additional","affiliation":[{"name":"Laboratoire Inflammation Tissus Epith\u00e9liaux et Cytokines (LITEC), Universit\u00e9 de Poitiers, 86000 Poitiers, France"},{"name":"Service Immunologie et Inflammation, Centre Hospitalier Universitaire de Poitiers, 86021 Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Favot","sequence":"additional","affiliation":[{"name":"Laboratoire Inflammation Tissus Epith\u00e9liaux et Cytokines (LITEC), Universit\u00e9 de Poitiers, 86000 Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,30]]},"reference":[{"key":"ref_1","first-page":"CD006990","article-title":"Surgical interventions for chronic rhinosinusitis with nasal polyps","volume":"11","author":"Sharma","year":"2014","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.anorl.2020.12.002","article-title":"Biotherapy and treatment of adult primary chronic rhinosinusitis with nasal polyps: Cellular and molecular bases","volume":"138","author":"Bartier","year":"2020","journal-title":"Eur. Ann. Otorhinolaryngol. Head Neck Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.jaci.2015.12.1324","article-title":"Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers","volume":"137","author":"Tomassen","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1097\/ACI.0b013e3282f4178f","article-title":"Role of staphylococcal superantigens in upper airway disease","volume":"8","author":"Bachert","year":"2008","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1097\/00005537-200308000-00020","article-title":"The Effect of Nasal Polyp Epithelial Cells on Eosinophil Activation","volume":"113","author":"Shin","year":"2003","journal-title":"Laryngoscope"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1111\/j.1398-9995.2008.01785.x","article-title":"How epithelial cells detect danger: Aiding the immune response","volume":"63","author":"Vroling","year":"2008","journal-title":"Allergy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1093\/intimm\/11.11.1819","article-title":"Th2 cytokine dependence of IgD production by normal human B cells","volume":"11","author":"Lelievre","year":"1999","journal-title":"Int. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1840","DOI":"10.1111\/j.1365-2222.2007.02838.x","article-title":"Local immunoglobulin production in nasal polyposis is modulated by superantigens","volume":"37","author":"Gevaert","year":"2007","journal-title":"Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"375","DOI":"10.3346\/jkms.2002.17.3.375","article-title":"Role of IgG, IgA, and IgE Antibodies in Nasal Polyp Tissue: Their Relationships with Eosinophilic Infiltration and Degranulation","volume":"17","author":"Suh","year":"2002","journal-title":"J. Korean Med. Sci."},{"key":"ref_10","first-page":"235","article-title":"IL-4 and TNF-alpha increased the secretion of eotaxin from cultured fibroblasts of nasal polyps with eosinophil infiltration","volume":"45","author":"Yoshifuku","year":"2007","journal-title":"Rhinology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1165\/rcmb.2003-0071OC","article-title":"Characterization of Interleukin-4\u2013Stimulated Nasal Polyp Fibroblasts","volume":"30","author":"Steinke","year":"2004","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/alr.21298","article-title":"Interleukin-4 and interleukin-13 compromise the sinonasal epithelial barrier and perturb intercellular junction protein expression","volume":"4","author":"Wise","year":"2014","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1002\/alr.21158","article-title":"Sinonasal epithelial wound resealing in an in vitro model: Inhibition of wound closure with IL-4 exposure","volume":"3","author":"Wise","year":"2013","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1001\/jama.2015.19330","article-title":"Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients with Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial","volume":"315","author":"Bachert","year":"2016","journal-title":"JAMA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1146\/annurev-pathol-052016-100401","article-title":"Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis","volume":"12","author":"Schleimer","year":"2017","journal-title":"Annu. Rev. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"123","DOI":"10.2147\/JAA.S52387","article-title":"Dupilumab: A novel treatment for asthma","volume":"7","author":"Vatrella","year":"2014","journal-title":"J. Asthma Allergy"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jaci.2011.03.017","article-title":"Increased expression of the chemokine CCL23 in eosinophilic chronic rhinosinusitis with nasal polyps","volume":"128","author":"Poposki","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"279","DOI":"10.2500\/105065800781329573","article-title":"Nasal Polyposis: From Cytokines to Growth","volume":"14","author":"Bachert","year":"2000","journal-title":"Am. J. Rhinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1080\/00016480600951368","article-title":"Eosinophil infiltration and activation in nasal polyposis","volume":"127","author":"Fan","year":"2007","journal-title":"Acta Oto-Laryngol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.2500\/105065898782103007","article-title":"Cytokines and adhesion molecules in allergic rhinitis","volume":"12","author":"Bachert","year":"1998","journal-title":"Am. J. Rhinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1111\/j.1365-2222.1995.tb01108.x","article-title":"Cytokine gene expression and release from epithelial cells. A comparison study between healthy nasal mucosa and nasal polyps","volume":"25","author":"Mullou","year":"1995","journal-title":"Clin. Exp. Allergy J. Br. Soc. Allergy Clin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0196-0709(97)90003-X","article-title":"Interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor expression in nasal polyps","volume":"18","author":"Allen","year":"1997","journal-title":"Am. J. Otolaryngol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.2147\/TCRM.S111862","article-title":"Role of biologics in severe eosinophilic asthma\u2014Focus on reslizumab","volume":"12","author":"Pelaia","year":"2016","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1007\/s00405-008-0872-9","article-title":"Clinical significance of eosinophilic cationic protein levels in nasal secretions of patients with nasal polyposis","volume":"266","author":"Sun","year":"2009","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1182\/blood.V96.6.2163","article-title":"Interleukin-9 enhances interleukin-5 receptor expression, differentiation, and survival of human eosinophils","volume":"96","author":"Gounni","year":"2000","journal-title":"Blood"},{"key":"ref_26","first-page":"233","article-title":"Interleukin-9 stimulates the production of interleukin-5 in CD4+ T cells","volume":"16","author":"Poulin","year":"2005","journal-title":"Eur. Cytokine Netw."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Parker, J.C., Thavagnanam, S., Skibinski, G., Lyons, J., Bell, J., Heaney, L.G., and Shields, M.D. (2013). Chronic IL9 and IL-13 Exposure Leads to an Altered Differentiation of Ciliated Cells in a Well-Differentiated Paediatric Bronchial Epithelial Cell Model. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061023"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"186","DOI":"10.4168\/aair.2011.3.3.186","article-title":"Increased Expression and Role of Thymic Stromal Lymphopoietin in Nasal Polyposis","volume":"3","author":"Kimura","year":"2011","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/MAJ.0b013e3181f20489","article-title":"Role of Thymic Stromal Lymphopoietin in the Pathogenesis of Nasal Polyposis","volume":"341","author":"Liu","year":"2011","journal-title":"Am. J. Med. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1159\/000346929","article-title":"Clinical Characteristics and Expression of Thymic Stromal Lymphopoetin in Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis","volume":"75","author":"Ouyang","year":"2013","journal-title":"ORL J. Oto-Rhino-Laryngol. Its Relat. Spec."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1001\/archotol.132.3.285","article-title":"Increased Prevalence of Interleukin-1 Receptor Antagonist Gene Polymorphism in Patients with Chronic Rhinosinusitis","volume":"132","author":"Cheng","year":"2006","journal-title":"Arch. Otolaryngol.-Head Neck Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1001\/archoto.2009.219","article-title":"Association of IL1A, IL1B, and TNF Gene Polymorphisms With Chronic Rhinosinusitis With and Without Nasal Polyposis: A replication study","volume":"136","author":"Endam","year":"2010","journal-title":"Arch. Otolaryngol.-Head Neck Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0385-8146(00)00052-3","article-title":"Expression of RANTES by IL-1 \u03b2 and TNF-\u03b1 stimulated nasal polyp fibroblasts","volume":"27","author":"Saji","year":"2000","journal-title":"Auris Nasus Larynx"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12950-014-0046-z","article-title":"Interleukin-1\u03b2 regulates the expression of glucocorticoid receptor isoforms in nasal polyps in vitro via p38 MAPK and JNK signal transduction pathways","volume":"12","author":"Wang","year":"2015","journal-title":"J. Inflamm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1164\/rccm.200805-666OC","article-title":"Resolution of Allergic Inflammation and Airway Hyperreactivity Is Dependent upon Disruption of the T1\/ST2\u2013IL-33 Pathway","volume":"179","author":"Kearley","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.jdermsci.2013.04.014","article-title":"Expression of IL-33 in the epidermis: The mechanism of induction by IL-17","volume":"71","author":"Meephansan","year":"2013","journal-title":"J. Dermatol. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1136\/thoraxjnl-2016-208772","article-title":"The role of interleukin-33 in chronic rhinosinusitis","volume":"72","author":"Kim","year":"2017","journal-title":"Thorax"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.cyto.2016.10.010","article-title":"Interleukin-33 induces mucin gene expression and goblet cell hyperplasia in human nasal epithelial cells","volume":"90","author":"Ishinaga","year":"2017","journal-title":"Cytokine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1001\/archotol.133.7.705","article-title":"Proinflammatory Cytokine Single Nucleotide Polymorphisms in Nasal Polyposis","volume":"133","author":"Erbek","year":"2007","journal-title":"Arch. Otolaryngol.-Head Neck Surg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.anl.2006.05.008","article-title":"TNF-\u03b1 upregulates VCAM-1 and NF-\u03baB in fibroblasts from nasal polyps","volume":"34","author":"Ohori","year":"2007","journal-title":"Auris Nasus Larynx"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"251","DOI":"10.2500\/ajr.2007.21.2958","article-title":"Tumor Necrosis Factor-\u03b1 Stimulates the Expression of C-C Chemokine Ligand 2 Gene in Fibroblasts from the Human Nasal Polyp through the Pathways of Mitogen-Activated Protein Kinase","volume":"21","author":"Lin","year":"2007","journal-title":"Am. J. Rhinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1365-3083.2006.01750.x","article-title":"Interleukin-6 Trans-Signalling in Chronic Inflammation and Cancer","volume":"63","author":"Scheller","year":"2006","journal-title":"Scand. J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s12967-020-02309-9","article-title":"Pathogenesis of chronic rhinosinusitis with nasal polyps: Role of IL-6 in airway epithelial cell dysfunction","volume":"18","author":"Bequignon","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.jaci.2015.01.043","article-title":"Oncostatin M promotes mucosal epithelial barrier dysfunction, and its expression is increased in patients with eosinophilic mucosal disease","volume":"136","author":"Pothoven","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/ni1497","article-title":"Development, cytokine profile and function of human interleukin 17\u2013producing helper T cells","volume":"8","author":"Wilson","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.jaci.2015.01.003","article-title":"IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis","volume":"135","author":"Shin","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"175","DOI":"10.2500\/ajra.2015.29.4176","article-title":"Interleukin-25 and Interleukin-33 as Mediators of Eosinophilic Inflammation in Chronic Rhinosinusitis","volume":"29","author":"Lam","year":"2015","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"980","DOI":"10.4168\/aair.2020.12.6.980","article-title":"Enhanced Type 2 Immune Reactions by Increased IL-22\/IL-22Ra1 Signaling in Chronic Rhinosinusitis with Nasal Polyps","volume":"12","author":"Kim","year":"2020","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.alit.2016.04.017","article-title":"IL-22\/IL-22R1 signaling regulates the pathophysiology of chronic rhinosinusitis with nasal polyps via alteration of MUC1 expression","volume":"66","author":"Noyama","year":"2017","journal-title":"Allergol. Int."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Xu, J., Han, R., Kim, D.W., Mo, J.-H., Jin, Y., Rha, K.-S., and Kim, Y.M. (2016). Role of Interleukin-10 on Nasal Polypogenesis in Patients with Chronic Rhinosinusitis with Nasal Polyps. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161013"},{"key":"ref_51","first-page":"131","article-title":"Interleukin-32","volume":"22","author":"Kim","year":"2005","journal-title":"Immunity"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.cyto.2009.10.003","article-title":"Suppressing IL-32 in monocytes impairs the induction of the proinflammatory cytokines TNF\u03b1 and IL-1\u03b2","volume":"49","author":"Hong","year":"2010","journal-title":"Cytokine"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1046\/j.1365-2222.2000.00095.x","article-title":"Epithelial damage and response","volume":"30","author":"Holgate","year":"2000","journal-title":"Clin. Exp. Allergy"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1084\/jem.179.3.1041","article-title":"Transforming growth factor beta abrogates the effects of hematopoietins on eosinophils and induces their apoptosis","volume":"179","author":"Alam","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.imlet.2006.01.003","article-title":"The effect of transforming growth factor (TGF)-\u03b21 and (TGF)-\u03b22 on nasal polyp fibroblast activities involved upper airway remodeling: Modulation by fluticasone propionate","volume":"105","author":"Serpero","year":"2006","journal-title":"Immunol. Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1159\/000497829","article-title":"TGF-\u03b21 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21","volume":"179","author":"Li","year":"2019","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1177\/194589240401800502","article-title":"Transforming growth factor beta1 in nasal remodeling: Differences between chronic rhinosinusitis and nasal polyposis","volume":"18","author":"Watelet","year":"2004","journal-title":"Am. J. Rhinol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1189\/jlb.0603252","article-title":"Interferon-\u03b3: An overview of signals, mechanisms and functions","volume":"75","author":"Schroder","year":"2004","journal-title":"J. Leukoc. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1177\/019459989411100111","article-title":"Accumulation of Interferon Gamma-Producing TH1 Helper T Cells in Nasal Polyps","volume":"111","author":"Miller","year":"1994","journal-title":"Otolaryngol. Neck Surg."},{"key":"ref_60","first-page":"509","article-title":"The role of interleukin-2 pathway in pathogenesis of nasal polyps","volume":"28","author":"Wang","year":"2014","journal-title":"Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi J. Clin. Otorhinolaryngol. Head Neck Surg."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1111\/all.14550","article-title":"Extent of inflammation in severe nasal polyposis and effect of sinus surgery on inflammation","volume":"76","author":"Jonstam","year":"2021","journal-title":"Allergy"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1146\/annurev-immunol-031210-101317","article-title":"Immunoglobulin Responses at the Mucosal Interface","volume":"29","author":"Cerutti","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhino12.000","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2012","volume":"50","author":"Fokkens","year":"2012","journal-title":"Rhinology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1159\/000110085","article-title":"Induction of TARC Production by Lipopolysaccharide and Interleukin-4 in Nasal Fibroblasts","volume":"145","author":"Fukumoto","year":"2008","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.2147\/TCRM.S125964","article-title":"Dupilumab in the management of moderate-to-severe asthma: The data so far","volume":"13","author":"Barranco","year":"2017","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1002\/alr.22630","article-title":"Interleukin 13 (IL-13) alters hypoxia-associated genes and upregulates CD73","volume":"10","author":"Khalil","year":"2020","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1177\/194589240501900202","article-title":"Expression of Interleukin-5, Interleukin-8, and Interleukin-10 mRNA in the Osteomeatal Complex in Nasal Polyposis","volume":"19","author":"Chen","year":"2005","journal-title":"Am. J. Rhinol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S0091-6749(97)80019-X","article-title":"IL-5 synthesis is upregulated in human nasal polyp tissue1","volume":"99","author":"Bachert","year":"1997","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"383","DOI":"10.2500\/105065898780708008","article-title":"Cytokines in Nasal Polyposis, Acute and Chronic Sinusitis","volume":"12","author":"Rudack","year":"1998","journal-title":"Am. J. Rhinol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1172\/JCI0213696","article-title":"Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology","volume":"109","author":"Temann","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.anai.2015.01.012","article-title":"Immune profile modulation of blood and mucosal eosinophils in nasal polyposis with concomitant asthma","volume":"114","author":"Mortuaire","year":"2015","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/ni805","article-title":"Human epithelial cells trigger dendritic cell\u2013mediated allergic inflammation by producing TSLP","volume":"3","author":"Soumelis","year":"2002","journal-title":"Nat. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1111\/all.14526","article-title":"Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation","volume":"75","author":"Hong","year":"2020","journal-title":"Allergy"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.4049\/jimmunol.179.2.1080","article-title":"TLR3- and Th2 cytokine-dependent production of thymic stromal lymphopoietin in human airway epithelial cells","volume":"17","author":"Kato","year":"2007","journal-title":"J. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.4049\/jimmunol.0900904","article-title":"Proteases Induce Production of Thymic Stromal Lymphopoietin by Airway Epithelial Cells through Protease-Activated Receptor-2","volume":"183","author":"Kouzaki","year":"2009","journal-title":"J. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.1111\/all.15089","article-title":"Advances and highlights in biomarkers of allergic diseases","volume":"76","author":"Ogulur","year":"2021","journal-title":"Allergy"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.alit.2014.12.006","article-title":"Immunopathology of chronic rhinosinusitis","volume":"64","author":"Kato","year":"2015","journal-title":"Allergol. Int. Off. J. Jpn. Soc. Allergol."},{"key":"ref_78","first-page":"29","article-title":"Interleukin-33: A novel mediator with a role in distinct disease pathologies: Key Symposium: The biology of IL-33","volume":"269","author":"Hueber","year":"2010","journal-title":"J. Intern. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/imr.12619","article-title":"Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family","volume":"281","author":"Cayrol","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"E115","DOI":"10.1002\/lary.24462","article-title":"Expression of IL-33 and its receptor ST2 in chronic rhinosinusitis with nasal polyps: IL-33 and ST2 in Chronic Rhinosinusitis","volume":"124","author":"Baba","year":"2014","journal-title":"Laryngoscope"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1164\/rccm.201212-2227OC","article-title":"IL-33\u2013Responsive Innate Lymphoid Cells Are an Important Source of IL-13 in Chronic Rhinosinusitis with Nasal Polyps","volume":"188","author":"Shaw","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1002\/lary.28000","article-title":"Aspergillus fumigatusinduction of IL-33 expression in chronic rhinosinusitis is PAR2-dependent","volume":"129","author":"Dietz","year":"2019","journal-title":"Laryngoscope"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1398-9995.2011.02735.x","article-title":"Anti-IL-33 antibody has a therapeutic effect in a murine model of allergic rhinitis: Effect of anti-IL-33 on murine allergy","volume":"67","author":"Kim","year":"2011","journal-title":"Allergy"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.cyto.2016.08.014","article-title":"Molecular mechanisms of action of anti-TNF-\u03b1 agents\u2014Comparison among therapeutic TNF-\u03b1 antagonists","volume":"101","author":"Mitoma","year":"2018","journal-title":"Cytokine"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1042\/CS20110340","article-title":"IL-6\/IL-6 receptor system and its role in physiological and pathological conditions","volume":"122","author":"Mihara","year":"2011","journal-title":"Clin. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1042\/bj3000281","article-title":"Soluble receptors for cytokines and growth factors: Generation and biological function","volume":"300","author":"Heinrich","year":"1994","journal-title":"Biochem. J."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jaci.2009.10.072","article-title":"Evidence for altered activity of the IL-6 pathway in chronic rhinosinusitis with nasal polyps","volume":"125","author":"Peters","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_88","first-page":"4615","article-title":"Oncostatin M Secreted by Skin Infiltrating T Lymphocytes Is a Potent Keratinocyte Activator Involved in Skin Inflammation","volume":"178","author":"Boniface","year":"2007","journal-title":"J. Immunol. Baltim. Md. 1950"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Hanlon, M.M., Rakovich, T., Cunningham, C.C., Ansboro, S., Veale, D., Fearon, U., and McGarry, T. (2019). STAT3 Mediates the Differential Effects of Oncostatin M and TNF\u03b1 on RA Synovial Fibroblast and Endothelial Cell Function. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02056"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"7243","DOI":"10.4049\/jimmunol.181.10.7243","article-title":"Mechanisms of Oncostatin M-Induced Pulmonary Inflammation and Fibrosis","volume":"181","author":"Mozaffarian","year":"2008","journal-title":"J. Immunol."},{"key":"ref_91","first-page":"308","article-title":"Serum levels of interleukin 6 (IL-6), oncostatin M, soluble IL-6 receptor, and soluble gp130 in patients with systemic sclerosis","volume":"25","author":"Hasegawa","year":"1998","journal-title":"J. Rheumatol."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Rabeony, H., Petit-Paris, I., Garnier, J., Barrault, C., Pedretti, N., Guilloteau, K., J\u00e9gou, J.-F., Guillet, G., Huguier, V., and Lecron, J.-C. (2014). Inhibition of Keratinocyte Differentiation by the Synergistic Effect of IL-17A, IL-22, IL-1\u03b1, TNF\u03b1 and Oncostatin, M. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0101937"},{"key":"ref_93","first-page":"5263","article-title":"Skin Inflammation Induced by the Synergistic Action of IL-17A, IL-22, Oncostatin M, IL-1\u03b1, and TNF-\u03b1 Recapitulates Some Features of Psoriasis","volume":"184","author":"Guilloteau","year":"2010","journal-title":"J. Immunol. Baltim. Md. 1950"},{"key":"ref_94","first-page":"412","article-title":"Expression of IL-17 and syndecan-1 in nasal polyps and their correlation with nasal polyps","volume":"37","author":"Gong","year":"2017","journal-title":"Acta Acad. Med. Wuhan"},{"key":"ref_95","first-page":"53","article-title":"The expression and significance of interleukin-17 and the infiltrating eosinophils in nasal polyps and nasal mucous of allergic rhinitis","volume":"24","author":"Ba","year":"2010","journal-title":"Lin Chuang Yan Hou Tou Jing Wai Ke Za zhi J. Clin. Otorhinolaryngol. Head Neck Surg."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.jaci.2019.06.023","article-title":"Cross-talk between TH2 and TH17 pathways in patients with chronic rhinosinusitis with nasal polyps","volume":"144","author":"Wang","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/S1074-7613(01)00243-6","article-title":"IL-25 Induces IL-4, IL-5, and IL-13 and Th2-Associated Pathologies In Vivo","volume":"15","author":"Fort","year":"2001","journal-title":"Immunity"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1074\/jbc.M008289200","article-title":"IL-17E, a Novel Proinflammatory Ligand for the IL-17 Receptor Homolog IL-17Rh1","volume":"276","author":"Lee","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.4049\/jimmunol.1200461","article-title":"Epithelial cell-derived IL-25, but not Th17 cell-derived IL-17 or IL-17F, is crucial for murine asthma","volume":"189","author":"Suzukawa","year":"2012","journal-title":"J. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature16161","article-title":"Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit","volume":"529","author":"Ji","year":"2016","journal-title":"Nature"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"256ra134","DOI":"10.1126\/scitranslmed.3009124","article-title":"Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation","volume":"6","author":"Beale","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1084\/jem.20061675","article-title":"Interleukin 25 promotes the initiation of proallergic type 2 responses","volume":"204","author":"Angkasekwinai","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1084\/jem.20070406","article-title":"IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC\u2013activated Th2 memory cells","volume":"204","author":"Wang","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/imr.12027","article-title":"IL-22, not simply a Th17 cytokine","volume":"252","author":"Rutz","year":"2013","journal-title":"Immunol. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/ni.2025","article-title":"Border patrol: Regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22","volume":"12","author":"Sonnenberg","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3695","DOI":"10.4049\/jimmunol.174.6.3695","article-title":"IL-22 Inhibits Epidermal Differentiation and Induces Proinflammatory Gene Expression and Migration of Human Keratinocytes","volume":"174","author":"Boniface","year":"2005","journal-title":"J. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.1016\/j.jaci.2020.11.037","article-title":"Mechanisms and biomarkers of inflammatory endotypes in chronic rhinosinusitis without nasal polyps","volume":"147","author":"Klingler","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/s00405-005-1031-1","article-title":"Davidsson, \u00c5ke Interleukin 5, IL6, IL12, IFN-\u03b3, RANTES and Fractalkine in human nasal polyps, turbinate mucosa and serum","volume":"263","author":"Danielsen","year":"2006","journal-title":"Arch. Oto-Rhino-Laryngol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1111\/j.1398-9995.2006.01225.x","article-title":"Differentiation of chronic sinus diseases by measurement of inflammatory mediators","volume":"61","author":"Claeys","year":"2006","journal-title":"Allergy"},{"key":"ref_110","first-page":"297","article-title":"T helper cell population and eosinophilia in nasal polyps","volume":"17","author":"Cheng","year":"2007","journal-title":"J. Investig. Allergol. Clin. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.otohns.2003.12.022","article-title":"Lymphocyte Subpopulations and Cytokines in Nasal Polyps: Is there a Local Immune System in the Nasal Polyp?","volume":"130","author":"Bernstein","year":"2004","journal-title":"Otolaryngol. Neck Surg."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1615\/CritRevImmunol.v32.i1.30","article-title":"Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune Disease","volume":"32","author":"Iyer","year":"2012","journal-title":"Crit. Rev. Immunol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev-immunol-031210-101312","article-title":"Regulation and Functions of the IL-10 Family of Cytokines in Inflammation and Disease","volume":"29","author":"Ouyang","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1046\/j.1365-2567.2001.01235.x","article-title":"Mechanisms of interleukin-10-mediated immune suppression","volume":"103","author":"Akdis","year":"2001","journal-title":"Immunology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/j.1600-065X.2008.00706.x","article-title":"Interleukin-10: New perspectives on an old cytokine","volume":"226","author":"Mosser","year":"2008","journal-title":"Immunol. Rev."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1684\/ecn.2019.0434","article-title":"IL-10 induces TGF-\u03b2 secretion, TGF-\u03b2 receptor II upregulation, and IgA secretion in B cells","volume":"30","author":"Bagheri","year":"2019","journal-title":"Eur. Cytokine Netw."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.jaci.2014.10.058","article-title":"Staphylococcal protein A\u2013formulated immune complexes suppress enterotoxin-induced cellular responses in nasal polyps","volume":"136","author":"Okano","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1097\/MLG.0b013e318159cc0b","article-title":"Dual Action of TGF-\u03b21 on Nasal-Polyp Derived Fibroblasts","volume":"118","author":"Little","year":"2008","journal-title":"Laryngoscope"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"S254","DOI":"10.1080\/21691401.2018.1491477","article-title":"Hyaluronan antagonizes the differentiation effect of TGF-\u03b21 on nasal epithelial cells through down-regulation of TGF-\u03b2 type I receptor","volume":"46","author":"Huang","year":"2018","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1111\/j.1398-9995.2009.02003.x","article-title":"Muco-ciliary differentiation of nasal epithelial cells is decreased after wound healingin vitro","volume":"64","author":"Lazard","year":"2009","journal-title":"Allergy"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1001\/archotol.124.12.1361","article-title":"Expression of the transforming growth factor beta isoforms in inflammatory cells of nasal polyps","volume":"124","author":"Coste","year":"1998","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"iii61","DOI":"10.1136\/ard.2006.058511","article-title":"IL-32, a novel cytokine with a possible role in disease","volume":"65","author":"Dinarello","year":"2006","journal-title":"Ann. Rheum. Dis."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1111\/j.1398-9995.2012.02820.x","article-title":"Regulation and expression of IL-32 in chronic rhinosinusitis","volume":"67","author":"Soyka","year":"2012","journal-title":"Allergy"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1398-9995.2011.02706.x","article-title":"Differential expression of interleukin-32 in chronic rhinosinusitis with and without nasal polyps: Expression of interleukin-32 in chronic rhinosinusitis","volume":"67","author":"Keswani","year":"2011","journal-title":"Allergy"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/alr.21792","article-title":"Toll-like receptor 4-mediated expression of interleukin-32 via the c-Jun N-terminal kinase\/protein kinase B\/cyclic adenosine monophosphate response element binding protein pathway in chronic rhinosinusitis with nasal polyps: IL-32 in CRS with nasal polyps","volume":"6","author":"Cho","year":"2016","journal-title":"Int. Forum Allergy Rhinol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/417\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:56:25Z","timestamp":1760169385000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,30]]},"references-count":125,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23010417"],"URL":"https:\/\/doi.org\/10.3390\/ijms23010417","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,30]]}}}