{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T03:33:52Z","timestamp":1794022432211,"version":"4.8.0"},"reference-count":127,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic rhinosinusitis (CRS), whose prevalence and pathogenesis are age-related, is characterized by nasal tissue eosinophil infiltration. CD40-CD40 ligand (CD40L) pathway involves in the eosinophil-mediated inflammation, and inducible co-stimulator (ICOS)\u2013ICOS ligand (ICOSL) signal can strengthen CD40-CD40L interaction. Whether CD40-CD40L and ICOS-ICOSL have a role in the development of CRS remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The aim of this study is to investigate the association of CD40-CD40L and ICOS-ICOSL expression with CRS and underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Immunohistology detected the expression of CD40, CD40L, ICOS, and ICOSL. Immunofluorescence was performed to evaluate the co-localizations of CD40 or ICOSL with eosinophils. Correlations between CD40-CD40L and ICOS-ICOSL as well as clinical parameters were analyzed. Flow cytometry was used to explore the activation of eosinophils by CD69 expression and the CD40 and ICOSL expression on eosinophils.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the non-eCRS subset, ECRS (eosinophilic CRS) subset showed significantly increased CD40, ICOS, and ICOSL expression. The CD40, CD40L, ICOS, and ICOSL expressions were all positively correlated with eosinophil infiltration in nasal tissues. CD40 and ICOSL were mainly expressed on eosinophils. ICOS expression was significantly correlated with the expression of CD40-CD40L, whereas ICOSL expression was correlated with CD40 expression. ICOS-ICOSL expression positively correlated with blood eosinophils count and disease severity. rhCD40L and rhICOS significantly enhanced the activation of eosinophils from patients with ECRS. Tumor necrosis factor\u2013\u03b1 (TNF-\u03b1) and interleukin-5 (IL-5) obviously upregulated CD40 expression on eosinophils, which was significantly inhibited by the p38 mitogen-activated protein kinase (MAPK) inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Increased CD40-CD40L and ICOS-ICOSL expressions in nasal tissues are linked to eosinophils infiltration and disease severity of CRS. CD40-CD40L and ICOS-ICOSL signals enhance eosinophils activation of ECRS. TNF-\u03b1 and IL-5 regulate eosinophils function by increasing CD40 expression partly\n                      <jats:italic>via<\/jats:italic>\n                      p38 MAPK activation in patients with CRS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2023.1171308","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T05:00:16Z","timestamp":1685595616000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Involvement of CD40-CD40L and ICOS-ICOSL in the development of chronic rhinosinusitis by targeting eosinophils"],"prefix":"10.3389","volume":"14","author":[{"given":"Aina","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushuang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanxia","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"176","DOI":"10.4168\/aair.2020.12.2.176","article-title":"Chinese Society of allergy and Chinese society of otorhinolaryngology-head and neck surgery guideline for chronic rhinosinusitis","volume":"12","author":"Liu","year":"2020","journal-title":"Allergy Asthma Immunol Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.03.024","article-title":"Rethinking neutrophils and eosinophils in chronic rhinosinusitis","volume":"148","author":"Delemarre","year":"2021","journal-title":"J Allergy Clin Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4193\/Rhin20.600","article-title":"European Position paper on rhinosinusitis and nasal polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.jaci.2011.12.002","article-title":"Age-related differences in the pathogenesis of chronic rhinosinusitis","volume":"129","author":"Cho","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/00016480252814199","article-title":"The estimated incidence of symptomatic nasal polyps","volume":"122","author":"Larsen","year":"2002","journal-title":"Acta Oto-Laryngol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2013.839380","article-title":"Chronic rhinosinusitis and age: Is the pathogenesis different","volume":"11","author":"Mahdavinia","year":"2013","journal-title":"Expert Rev Anti Infect Ther"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.02.002","article-title":"Incidence and associated premorbid diagnoses of patients with chronic rhinosinusitis","volume":"131","author":"Tan","year":"2013","journal-title":"J Allergy Clin Immun"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.02.036","article-title":"Endotypes and phenotypes of chronic rhinosinusitis: A practall document of the European academy of allergy and clinical immunology and the American academy of allergy, asthma & immunology","volume":"131","author":"Akdis","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.10.006","article-title":"Chronic rhinosinusitis: Endotypes, biomarkers, and treatment response","volume":"140","author":"Gurrola","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1159\/000126066","article-title":"Chronic rhinosinusitis: Risk factors for the recurrence of chronic rhinosinusitis based on 5-year follow-up after endoscopic sinus surgery","volume":"146","author":"Matsuwaki","year":"2008","journal-title":"Int Arch Allergy Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4193\/Rhino10.261","article-title":"Mucosal eosinophilia and recurrence of nasal polyps - new classification of chronic rhinosinusitis","volume":"49","author":"Nakayama","year":"2011","journal-title":"Rhinology"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2014.28.4024","article-title":"The importance of local eosinophilia in the surgical outcome of chronic rhinosinusitis: A 3-year prospective observational study","volume":"28","author":"Vlaminck","year":"2014","journal-title":"Am J Rhinol Allergy"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.otohns.2007.07.036","article-title":"Histological and immunological features of non-eosinophilic nasal polyps","volume":"137","author":"Kim","year":"2007","journal-title":"Otolaryngol Head Neck Surg"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.anl.2011.01.007","article-title":"New clinical diagnostic criteria for eosinophilic chronic rhinosinusitis","volume":"38","author":"Sakuma","year":"2011","journal-title":"Auris Nasus Larynx"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.05.041","article-title":"Diversity of T(H) cytokine profiles in patients with chronic rhinosinusitis: A multicenter study in Europe, Asia, and Oceania","volume":"138","author":"Wang","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2500\/ajra.2014.28.4003","article-title":"Histological characteristics of chronic rhinosinusitis with nasal polyps: Recent 10-year experience of a single center in daegu, Korea","volume":"28","author":"Shin","year":"2014","journal-title":"Am J Rhinol Allergy"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22234","article-title":"Changes in the clinical and histological characteristics of Chinese chronic rhinosinusitis with nasal polyps over 11 years","volume":"9","author":"Wang","year":"2019","journal-title":"Int Forum Allergy Rhinol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3930","article-title":"Clinical targeting of the tnf and tnfr superfamilies","volume":"12","author":"Croft","year":"2013","journal-title":"Nat Rev Drug Discovery"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.12.4494","article-title":"Activation of human b cells mediated through two distinct cell surface differentiation antigens, Bp35 and Bp50","volume":"83","author":"Clark","year":"1986","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90095-7","article-title":"The immune responses in Cd40-deficient mice: Impaired immunoglobulin class switching and germinal center formation","volume":"1","author":"Kawabe","year":"1994","journal-title":"Immunity"},{"key":"B21","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/0090-1229(95)90135-3","article-title":"Cd40 expression by human fibroblasts","volume":"77","author":"Fries","year":"1995","journal-title":"Clin Immunol Immunopathol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1084\/jem.182.1.33","article-title":"Expression of functional Cd40 by vascular endothelial cells","volume":"182","author":"Hollenbaugh","year":"1995","journal-title":"J Exp Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.4.643","article-title":"Cd40 is expressed and functional on neuronal cells","volume":"21","author":"Tan","year":"2002","journal-title":"EMBO J"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118603","article-title":"Cd40 expression by human peripheral blood eosinophils","volume":"97","author":"Ohkawara","year":"1996","journal-title":"J Clin Invest"},{"key":"B25","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1111\/cea.12304","article-title":"Increased local ige production induced by common aeroallergens and phenotypic alteration of mast cells in Chinese eosinophilic, but not non-eosinophilic, chronic rhinosinusitis with nasal polyps","volume":"44","author":"Cao","year":"2014","journal-title":"Clin Exp Allergy"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2004.00621.x","article-title":"Organization of secondary lymphoid tissue and local ige formation to staphylococcus aureus enterotoxins in nasal polyp tissue","volume":"60","author":"Gevaert","year":"2005","journal-title":"Allergy"},{"key":"B27","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1111\/all.12054","article-title":"Local receptor revision and class switching to ige in chronic rhinosinusitis with nasal polyps","volume":"68","author":"Gevaert","year":"2013","journal-title":"Allergy"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12287","article-title":"Local increase in ige and class switch recombination to ige in nasal polyps in chronic rhinosinusitis","volume":"44","author":"Baba","year":"2014","journal-title":"Clin Exp Allergy"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1016\/j.jaci.2013.01.043","article-title":"Chronic rhinosinusitis with nasal polyps is characterized by b-cell inflammation and ebv-induced protein 2 expression","volume":"131","author":"Hulse","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s001090050129","article-title":"Molecular regulation of human ige synthesis","volume":"75","author":"Worm","year":"1997","journal-title":"J Mol Med (Berl)"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.8.3730","article-title":"Interleukin 13 induces interleukin 4-independent Igg4 and ige synthesis and Cd23 expression by human b cells","volume":"90","author":"Punnonen","year":"1993","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.6.1861","article-title":"Cd40 and ige: Synergism between anti-Cd40 monoclonal antibody and interleukin 4 in the induction of ige synthesis by highly purified human b cells","volume":"172","author":"Jabara","year":"1990","journal-title":"J Exp Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"8","DOI":"10.4049\/jimmunol.147.1.8","article-title":"Anti-Cd40 monoclonal antibodies or Cd4+ T cell clones and il-4 induce Igg4 and ige switching in purified human b cells Via different signaling pathways","volume":"147","author":"Gascan","year":"1991","journal-title":"J Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/35051107","article-title":"Icos is critical for Cd40-mediated antibody class switching","volume":"409","author":"McAdam","year":"2001","journal-title":"Nature"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00764.x","article-title":"The role of costimulation in antibody deficiencies: Icos and common variable immunodeficiency","volume":"229","author":"Yong","year":"2009","journal-title":"Immunol Rev"},{"key":"B36","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.jaci.2009.05.017","article-title":"Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese","volume":"124","author":"Cao","year":"2009","journal-title":"J Allergy Clin Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.1993.tb03313.x","article-title":"Measurement of Co-localization of objects in dual-colour confocal images","volume":"169","author":"Manders","year":"1993","journal-title":"J Microsc"},{"key":"B38","doi-asserted-by":"publisher","first-page":"BSR20193101","DOI":"10.1042\/BSR20193101","article-title":"Comparative analysis of inflammatory signature profiles in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyposis","volume":"40","author":"Yao","year":"2020","journal-title":"Biosci Rep"},{"key":"B39","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1002\/alr.22083","article-title":"Distinct gene expression profiles and regulation networks of nasal polyps in eosinophilic and non-eosinophilic chronic rhinosinusitis","volume":"8","author":"Okada","year":"2018","journal-title":"Int Forum Allergy Rhinol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.15.4.8879177","article-title":"Eosinophil infiltration in nonallergic chronic hyperplastic sinusitis with nasal polyposis (Chs\/Np) is associated with endothelial vcam-1 upregulation and expression of tnf-alpha","volume":"15","author":"Hamilos","year":"1996","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.10.4342","article-title":"Cd40 on human endothelial cells: Inducibility by cytokines and functional regulation of adhesion molecule expression","volume":"92","author":"Karmann","year":"1995","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.149.3.775","article-title":"Cd40 is functionally expressed on human thymic epithelial-cells","volume":"149","author":"Galy","year":"1992","journal-title":"J Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/s1074-7613(00)80117-x","article-title":"B7h, a novel costimulatory homolog of B7.1 and B7.2, is induced by tnfalpha","volume":"11","author":"Swallow","year":"1999","journal-title":"Immunity"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.092576699","article-title":"Icos-ligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory Cd4+ T cells","volume":"99","author":"Khayyamian","year":"2002","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108509200","article-title":"Tumor necrosis factor-alpha regulates the expression of inducible costimulator receptor ligand on Cd34(+) progenitor cells during differentiation into antigen presenting cells","volume":"276","author":"Richter","year":"2001","journal-title":"J Biol Chem"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830171210","article-title":"Recombinant human interleukin 5 is an eosinophil differentiation factor but has no activity in standard human b cell growth factor assays","volume":"17","author":"Clutterbuck","year":"1987","journal-title":"Eur J Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V73.6.1504.1504","article-title":"Human interleukin-5 (Il-5) regulates the production of eosinophils in human bone marrow cultures: Comparison and interaction with il-1, il-3, il-6, and gmcsf","volume":"73","author":"Clutterbuck","year":"1989","journal-title":"Blood"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V75.9.1774.bloodjournal7591774","article-title":"Regulation of human eosinophil precursor production by cytokines: A comparison of recombinant human interleukin-1 (Rhil-1), rhil-3, rhil-5, rhil-6, and Rh granulocyte-macrophage colony-stimulating factor","volume":"75","author":"Clutterbuck","year":"1990","journal-title":"Blood"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1159\/000053596","article-title":"Tumor necrosis factor-alpha mediates antiapoptotic signals partially Via P38 map kinase activation in human eosinophils","volume":"120","author":"Tsukahara","year":"1999","journal-title":"Int Arch Allergy Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1111\/all.12064","article-title":"Features of airway remodeling in different types of Chinese chronic rhinosinusitis are associated with inflammation patterns","volume":"68","author":"Shi","year":"2013","journal-title":"Allergy"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s10522-015-9628-2","article-title":"Compartmentalization of immunosenescence: A deeper look at the mucosa","volume":"17","author":"Martelli","year":"2016","journal-title":"Biogerontology"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1111\/cea.13586","article-title":"Age-associated changes in chronic rhinosinusitis endotypes","volume":"50","author":"Ryu","year":"2020","journal-title":"Clin Exp Allergy"},{"key":"B53","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s13073-018-0568-8","article-title":"Human genetic variants and age are the strongest predictors of humoral immune responses to common pathogens and vaccines","volume":"10","author":"Scepanovic","year":"2018","journal-title":"Genome Med"},{"key":"B54","doi-asserted-by":"publisher","first-page":"282","DOI":"10.3390\/medicina57030282","article-title":"Chronic rhinosinusitis with nasal polyps: Age and disease severity differences in the levels of inflammatory markers","volume":"57","author":"Vaitkus","year":"2021","journal-title":"Medicina-Lithuania"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2002.126781","article-title":"Cd40 engagement enhances eosinophil survival through induction of cellular inhibitor of apoptosis protein 2 expression: Possible involvement in allergic inflammation","volume":"110","author":"Bureau","year":"2002","journal-title":"J Allergy Clin Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830250335","article-title":"Cd40 ligand is functionally expressed on human eosinophils","volume":"25","author":"Gauchat","year":"1995","journal-title":"Eur J Immunol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1084\/jem.175.4.1091","article-title":"Identification of a novel surface protein on activated Cd4+ T cells that induces contact-dependent b cell differentiation (Help)","volume":"175","author":"Lederman","year":"1992","journal-title":"J Exp Med"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.14.6550","article-title":"A 39-kda protein on activated helper T cells binds Cd40 and transduces the signal for cognate activation of b cells","volume":"89","author":"Noelle","year":"1992","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B59","doi-asserted-by":"publisher","first-page":"180","DOI":"10.3892\/etm.2020.9310","article-title":"Immune cell infiltration and related core genes expression characteristics in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps","volume":"20","author":"Xiong","year":"2020","journal-title":"Exp Ther Med"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/16717","article-title":"Icos is an inducible T-cell Co-stimulator structurally and functionally related to Cd28","volume":"397","author":"Hutloff","year":"1999","journal-title":"Nature"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/45582","article-title":"T-Cell Co-stimulation through B7rp-1 and icos","volume":"402","author":"Yoshinaga","year":"1999","journal-title":"Nature"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1159\/000075612","article-title":"Icos: A new costimulatory Ligand\/Receptor pair and its role in T-cell activion","volume":"27","author":"Richter","year":"2004","journal-title":"Onkologie"},{"key":"B63","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1097\/ACI.0000000000000496","article-title":"Group 2 innate lymphoid cells and eosinophilic chronic rhinosinusitis","volume":"19","author":"Tojima","year":"2019","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.3390\/ijms21051843","article-title":"Clinical significance of cytoplasmic ige-positive mast cells in eosinophilic chronic rhinosinusitis","volume":"21","author":"Gion","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2017.05.019","article-title":"Distribution, subtype population, and ige positivity of mast cells in chronic rhinosinusitis with nasal polyps","volume":"119","author":"Baba","year":"2017","journal-title":"Ann Allergy Asthma Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.2500\/ar.2012.3.0030","article-title":"Relationships between il-17a and macrophages or Muc5ac in eosinophilic chronic rhinosinusitis and proposed pathological significance","volume":"3","author":"Ono","year":"2012","journal-title":"Allergy Rhinol (Providence)"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1111\/all.14627","article-title":"A murine model of eosinophilic chronic rhinosinusitis using the topical application of a vitamin D3 analog","volume":"76","author":"Kagoya","year":"2021","journal-title":"Allergy"},{"key":"B68","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1002\/lary.22507","article-title":"Diagnostic significance of blood eosinophil count in eosinophilic chronic rhinosinusitis with nasal polyps in Chinese adults","volume":"122","author":"Hu","year":"2012","journal-title":"Laryngoscope"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-014-2910-0","article-title":"Clinical characteristics and surrogate markers of eosinophilic chronic rhinosinusitis in southern China","volume":"271","author":"Zuo","year":"2014","journal-title":"Eur Arch Otorhinolaryngol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1017\/S0022215116009324","article-title":"Reduction of blood eosinophil counts in eosinophilic chronic rhinosinusitis after surgery","volume":"130","author":"Honma","year":"2016","journal-title":"J Laryngol Otol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2010.01.001","article-title":"Regulation of Cd4 T cell activation and effector function by inducible costimulator (Icos)","volume":"22","author":"Simpson","year":"2010","journal-title":"Curr Opin Immunol"},{"key":"B72","doi-asserted-by":"publisher","first-page":"55ra78","DOI":"10.1126\/scitranslmed.3000448","article-title":"The inducible costimulator (Icos) is critical for the development of human T(H)17 cells","volume":"2","author":"Paulos","year":"2010","journal-title":"Sci Transl Med"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M707693200","article-title":"T Helper cell-specific regulation of inducible costimulator expression Via distinct mechanisms mediated by T-bet and gata-3","volume":"283","author":"Tan","year":"2008","journal-title":"J Biol Chem"},{"key":"B74","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s41232-021-00164-9","article-title":"Differentiation, functions, and roles of T follicular regulatory cells in autoimmune diseases","volume":"41","author":"Hao","year":"2021","journal-title":"Inflammation Regener"},{"key":"B75","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1111\/imr.12771","article-title":"Inducible T-cell Co-stimulator: Signaling mechanisms in T follicular helper cells and beyond","volume":"291","author":"Panneton","year":"2019","journal-title":"Immunol Rev"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2019.11.002","article-title":"Increased Cd69 expression on activated eosinophils in eosinophilic chronic rhinosinusitis correlates with clinical findings","volume":"69","author":"Yun","year":"2020","journal-title":"Allergol Int"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1097\/01.mlg.0000147917.43615.c0","article-title":"Molecular and cellular staging for the severity of chronic rhinosinusitis","volume":"114","author":"Kountakis","year":"2004","journal-title":"Laryngoscope"},{"key":"B78","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1177\/1945892418768590","article-title":"Blood eosinophil and basophil values before and after surgery for eosinophilic-type sinonasal polyps","volume":"32","author":"Brescia","year":"2018","journal-title":"Am J Rhinol Allergy"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.2332\/allergolint.10-RAI-0202","article-title":"Pathological mechanisms and clinical features of eosinophilic chronic rhinosinusitis in the Japanese population","volume":"59","author":"Takeno","year":"2010","journal-title":"Allergol Int"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v2.i12.873","article-title":"Eosinophilic chronic rhinosinusitis in East asians","volume":"2","author":"Wang","year":"2014","journal-title":"World J Clin cases"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1186\/s12950-016-0121-8","article-title":"Pathogenesis of eosinophilic chronic rhinosinusitis","volume":"13","author":"Shah","year":"2016","journal-title":"J Inflammation (Lond)"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1592.2001.00228.x","article-title":"Mechanisms of eosinophilic inflammation in the mucosa of the nasal cavity paranasal sinus","volume":"50","author":"Terada","year":"2001","journal-title":"Allergol Int"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.4.2214","article-title":"Proinflammatory and Th2-derived cytokines modulate Cd40-mediated expression of inflammatory mediators in airway epithelia: Implications for the role of epithelial Cd40 in airway inflammation","volume":"165","author":"Propst","year":"2000","journal-title":"J Immunol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"698","DOI":"10.4049\/jimmunol.149.2.698","article-title":"Regulation of vascular cell adhesion molecule 1 on human dermal microvascular endothelial cells","volume":"149","author":"Swerlick","year":"1992","journal-title":"J Immunol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.6.1857","article-title":"Functional interactions of T cells with endothelial cells: The role of Cd40l-Cd40-Mediated signals","volume":"182","author":"Yellin","year":"1995","journal-title":"J Exp Med"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2003.139","article-title":"Chemokines in asthma: Cooperative interaction between chemokines and il-13","volume":"111","author":"Zimmermann","year":"2003","journal-title":"J Allergy Clin Immunol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.164.4.2009046","article-title":"The kinetics of allergen-induced eotaxin level in nasal lavage fluid: Its key role in eosinophil recruitment in nasal mucosa","volume":"164","author":"Terada","year":"2001","journal-title":"Am J Respir Crit Care Med"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.158.10.4670","article-title":"Cd40 is a functional activation antigen and B7-independent T cell costimulatory molecule on normal human lung fibroblasts","volume":"158","author":"Sempowski","year":"1997","journal-title":"J Immunol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/35393","article-title":"Cd40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells","volume":"391","author":"Henn","year":"1998","journal-title":"Nature"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.102","article-title":"Possible role for Cd40-Cd40l in the regulation of interstitial infiltration in the kidney","volume":"51","author":"van Kooten","year":"1997","journal-title":"Kidney Int"},{"key":"B91","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.coi.2016.08.003","article-title":"T Follicular helper cells in human autoimmunity","volume":"43","author":"Ueno","year":"2016","journal-title":"Curr Opin Immunol"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126311","article-title":"Th1-like icos+ Foxp3+ treg cells preferentially express Cxcr3 and home to B-islets during pre-diabetes in Bdc2.5 nod mice","volume":"10","author":"Kornete","year":"2015","journal-title":"PloS One"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.2002.01880.x","article-title":"Activation of P38 mitogen-activated protein kinase and nuclear factor-kappab in tumour necrosis factor-induced eotaxin release of human eosinophils","volume":"128","author":"Wong","year":"2002","journal-title":"Clin Exp Immunol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1006\/cyto.2001.0890","article-title":"Mechanism of tumour necrosis factor alpha mediated eosinophil survival","volume":"15","author":"Temkin","year":"2001","journal-title":"Cytokine"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2019.07.002","article-title":"Eosinophilic chronic rhinosinusitis","volume":"68","author":"Fujieda","year":"2019","journal-title":"Allergol Int"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1016\/j.jaci.2017.05.044","article-title":"Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial","volume":"140","author":"Bachert","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1177\/19458924211009429","article-title":"A phase ii, multicenter, randomized, placebo-controlled study of benralizumab, a humanized anti-Il-5r alpha monoclonal antibody, in patients with eosinophilic chronic rhinosinusitis","volume":"35","author":"Takabayashi","year":"2021","journal-title":"Am J Rhinol Allergy"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1080\/1744666x.2017.1298443","article-title":"Commonality of the il-4\/Il-13 pathway in atopic diseases","volume":"13","author":"Gandhi","year":"2017","journal-title":"Expert Rev Clin Immu"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.36.179","article-title":"Interleukin-13 but not interleukin-4 prolongs eosinophil survival and induces eosinophil chemotaxis","volume":"36","author":"Horie","year":"1997","journal-title":"Intern Med"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.20.3.3326","article-title":"Synergistic effects of interleukin-4 or interleukin-13 and tumor necrosis factor-alpha on eosinophil activation in vitro","volume":"20","author":"Luttmann","year":"1999","journal-title":"Am J Resp Cell Mol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12382362","article-title":"Il-4 induces chemotaxis of blood eosinophils from atopic dermatitis patients, but not from normal individuals","volume":"102","author":"Dubois","year":"1994","journal-title":"J Invest Dermatol"},{"key":"B102","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.148.4.1086","article-title":"IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1","volume":"148","author":"Schleimer","year":"1992","journal-title":"J Immunol"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.1998.tb03955.x","article-title":"The potential role of interleukin-13 in eosinophilic inflammation in nasal mucosa","volume":"53","author":"Terada","year":"1998","journal-title":"Allergy"},{"key":"B104","doi-asserted-by":"publisher","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-J Am Med Assoc"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2015.1119352","article-title":"Csl311, a novel, potent, therapeutic monoclonal antibody for the treatment of diseases mediated by the common beta chain of the il-3, gm-csf and il-5 receptors","volume":"8","author":"Panousis","year":"2016","journal-title":"Mabs-Austin"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2016.09.006","article-title":"Regulation of siglec-8-Induced intracellular reactive oxygen species production and eosinophil cell death by src family kinases","volume":"222","author":"Kano","year":"2017","journal-title":"Immunobiology"},{"key":"B107","doi-asserted-by":"publisher","first-page":"2227","DOI":"10.1016\/j.jaci.2018.10.066","article-title":"Sialic acid-binding immunoglobulin-like lectin (Siglec) 8 in patients with eosinophilic disorders: Receptor expression and targeting using chimeric antibodies","volume":"143","author":"Legrand","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5257","article-title":"Selective activation and functional significance of P38alpha mitogen-activated protein kinase in lipopolysaccharide-stimulated neutrophils","volume":"103","author":"Nick","year":"1999","journal-title":"J Clin Invest"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.12.6607","article-title":"Ikappabalpha degradation and nuclear factor-kappab DNA binding are insufficient for interleukin-1beta and tumor necrosis factor-Alpha-Induced kappab-dependent transcription. requirement for an additional activation pathway","volume":"273","author":"Bergmann","year":"1998","journal-title":"J Biol Chem"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.19.12422","article-title":"Activation of transcription factor nf-kappab and P38 mitogen-activated protein kinase is mediated by distinct and separate stress effector pathways","volume":"272","author":"Wesselborg","year":"1997","journal-title":"J Biol Chem"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1016\/s0014-5793(99)00683-3","article-title":"Cytokine-inducible Cd40 gene expression in vascular smooth muscle cells is mediated by nuclear factor kappab and signal transducer and activation of transcription-1","volume":"453","author":"Krzesz","year":"1999","journal-title":"FEBS Lett"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199905)42:5<871::Aid-anr5>3.0.Co;2-j","article-title":"Elevated levels and functional capacity of soluble Cd40 ligand in systemic lupus erythematosus sera","volume":"42","author":"Vakkalanka","year":"1999","journal-title":"Arthritis rheum"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa022600","article-title":"Soluble Cd40 ligand in acute coronary syndromes","volume":"348","author":"Heeschen","year":"2003","journal-title":"New Engl J Med"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1007\/s00384-002-0425-4","article-title":"Plasma levels of soluble Cd40 ligand are elevated in inflammatory bowel diseases","volume":"18","author":"Ludwiczek","year":"2003","journal-title":"Int J colorectal Dis"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2006.02.002","article-title":"Elevated levels of soluble Cd40 ligand (Scd40l) in serum of patients with systemic autoimmune diseases","volume":"26","author":"Goules","year":"2006","journal-title":"J Autoimmun"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-006-0389-9","article-title":"The levels of Scd30 and of Scd40l in a group of patients with systemic lupus erythematodes and their diagnostic value","volume":"26","author":"Cifersk\u00e1","year":"2007","journal-title":"Clin Rheumatol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjhyper.2006.06.007","article-title":"Enhanced plasma soluble Cd40 ligand levels in essential hypertensive patients with blunted nocturnal blood pressure decrease","volume":"20","author":"Desideri","year":"2007","journal-title":"Am J hypertension"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1172\/jci7014","article-title":"The soluble Cd40 ligand Scd154 in systemic lupus erythematosus","volume":"104","author":"Kato","year":"1999","journal-title":"J Clin Invest"},{"key":"B119","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1007\/978-0-387-89520-8_2","article-title":"Therapeutic interventions targeting Cd40l (Cd154) and Cd40: The opportunities and challenges","volume":"647","author":"Law","year":"2009","journal-title":"Adv Exp Med Biol"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1016\/j.revmed.2021.02.005","article-title":"[the Cd40-Cd40l axis: Current and future implications in clinical immunology]","volume":"42","author":"Vial","year":"2021","journal-title":"La Rev med interne"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1002\/art.10856","article-title":"A short course of Bg9588 (Anti-Cd40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis","volume":"48","author":"Boumpas","year":"2003","journal-title":"Arthritis rheum"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1002\/art.10273","article-title":"The effect of anti-Cd40 ligand antibody on b cells in human systemic lupus erythematosus","volume":"46","author":"Huang","year":"2002","journal-title":"Arthritis rheum"},{"key":"B123","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/nrrheum.2015.49","article-title":"Connective tissue diseases: Icos sustains pathogenic T-cell survival in sle mouse model","volume":"11","author":"Duarte","year":"2015","journal-title":"Nat Rev Rheumatol"},{"key":"B124","doi-asserted-by":"publisher","first-page":"491","DOI":"10.4049\/jimmunol.1502241","article-title":"Loss of immune tolerance is controlled by icos in Sle1 mice","volume":"197","author":"Mittereder","year":"2016","journal-title":"J Immunol"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/827480","article-title":"Increased frequency of circulating follicular helper T cells in patients with rheumatoid arthritis","volume":"2012","author":"Ma","year":"2012","journal-title":"Clin Dev Immunol"},{"key":"B126","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.jneuroim.2012.12.001","article-title":"Expansion of circulating counterparts of follicular helper T cells in patients with myasthenia gravis","volume":"256","author":"Luo","year":"2013","journal-title":"J neuroimmunol"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500759","article-title":"Circulating follicular regulatory T cells are defective in multiple sclerosis","volume":"195","author":"Dhaeze","year":"2015","journal-title":"J Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1171308\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T05:00:19Z","timestamp":1685595619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1171308\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,1]]},"references-count":127,"alternative-id":["10.3389\/fimmu.2023.1171308"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1171308","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,1]]},"article-number":"1171308"}}