{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:30:54Z","timestamp":1792661454272,"version":"4.5.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T00:00:00Z","timestamp":1676246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"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>Altered innate defense mechanisms, including an imbalance between oxidants and antioxidants release, have been implicated in the pathogenesis of chronic rhinosinusitis (CRS). The aim of this study is to investigate whether oxidative stress may attenuate the secretion of anti-viral interferons in human sinonasal mucosa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The levels of H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      in nasal secretion were increased in patients with CRS with nasal polyps, compared with that of CRS patients without nasal polyps and control subjects. Normal sinonasal epithelial cells derived from healthy subjects were cultured under an air-liquid interface. The cultured cells were infected with rhinovirus 16 (RV 16) or treated with poly (I: C), TLR3 agonist, after being pretreated with an oxidative stressor, H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      or antioxidant, N-acetylcysteine (NAC). Thereafter, the expression levels of type I (IFN-\u03b2) and type III (IFN-\u03bb1 and \u03bb2) interferons and interferon-stimulated genes (ISGs) were evaluated with RT-qPCR, ELISA, and western blot.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The data showed that the production of type I (IFN-\u03b2) and type III (IFN-\u03bb1 and \u03bb2) interferons and ISGs was upregulated in cells infected with RV 16 or treated with poly (I: C). However, their up-regulated expression was attenuated in cells pretreated with H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2,<\/jats:sub>\n                      but not inhibited in cells pretreated with NAC. In line with these data, the up-regulated expression of TLR3, RIG-1, MDA5, and IRF3 was reduced in cells pretreated with H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2,<\/jats:sub>\n                      but not attenuated in cells treated with NAC. Furthermore, cells transfected with Nrf2 siRNA showed decreased secretion of anti-viral interferons whereas sulforaphane treatment enhanced the secretory capacity of antiviral interferons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results suggest that the production of RV16-induced antiviral interferons may be attenuated by oxidative stress.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2023.1086381","type":"journal-article","created":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T02:19:01Z","timestamp":1676254741000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Hydrogen peroxide attenuates rhinovirus-induced anti-viral interferon secretion in sinonasal epithelial cells"],"prefix":"10.3389","volume":"14","author":[{"given":"Sang Hag","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mun Soo","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da Bin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u00a0Hyung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hyeok","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,13]]},"reference":[{"key":"B1","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":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/alr.22403","article-title":"Are rhinovirus implicated in the pathogenesis of sinusitis and chronic rhinosinusitis exacerbations? A comprehensive review","volume":"9","author":"Bashharat","year":"2019","journal-title":"Int Forum Allergy Rhinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.5812\/jjm.20068","article-title":"Prevalence of rhinovirus and respiratory syncytial virus among patients with chronic rhinosinusitis","volume":"8","author":"Abshirini","year":"2015","journal-title":"Jundishapur J Microbiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.1998.274.6.L1017","article-title":"Rhinovirus infection induces mucus hypersecretion","volume":"274","author":"Yuta","year":"1998","journal-title":"Am J Physiol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2021.1883965","article-title":"Airway tight junctions as targets of viral infections. tight junction and viral infection","volume":"9","author":"Linfield","year":"2021","journal-title":"Tissue Barriers"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-022-01542-w","article-title":"Wogonin inhibits tight junction disruption via suppression of inflammatory response and phosphorylation of AKT\/NF-\u03baB and ERK1\/2 in rhinovirus-infected human nasal epithelial cells","volume":"71","author":"Kim","year":"2022","journal-title":"Inflammation Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1086\/379833","article-title":"Effects of rhinovirus infection on the adherence of streptococcus pneumoniae to cultured human airway epithelial cells","volume":"188","author":"Ishizuka","year":"2003","journal-title":"J Infect Dis"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087262","article-title":"Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway","volume":"301","author":"Yamamoto","year":"2003","journal-title":"Science"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/ni1087","article-title":"The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses","volume":"5","author":"Yoneyama","year":"2004","journal-title":"Nat Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407639101","article-title":"The V proteinsof paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activationof the IFN-beta promoter","volume":"101","author":"Andrejeva","year":"2004","journal-title":"Proc Natl Acad Sci USA"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901386","article-title":"Role of double-stranded RNA pattern recognition receptors in rhinovirus induced airway epithelial cell responses","volume":"183","author":"Wang","year":"2009","journal-title":"J Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2006.02530.x","article-title":"Synthetic double-stranded RNA induces multiple genes related to inflammation through toll-like receptor 3 depending on NF-kappaB and\/or IRF-3 in airway epithelial cells","volume":"36","author":"Matsukura","year":"2006","journal-title":"Clin Exp Allergy"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/ni1303","article-title":"Innate immune recognition of viral infection","volume":"7","author":"Kawai","year":"2006","journal-title":"Nat Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041901","article-title":"Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus","volume":"201","author":"Wark","year":"2005","journal-title":"J Exp Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nm1462","article-title":"Role of deficient type III interferon-lambda production in asthma exacerbations","volume":"12","author":"Contoli","year":"2006","journal-title":"Nat Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00277","article-title":"Rhinovirus and innate immune function of airway epithelium","volume":"10","author":"Ganjian","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00974","article-title":"Airway epithelial cell immunity is delayed during rhinovirus infection in asthma and COPD","volume":"11","author":"Veerati","year":"2020","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/all.12627","article-title":"Th2 cytokines impair innate immune responses to rhinovirus in respiratory epithelial cells","volume":"70","author":"Contoli","year":"2015","journal-title":"Allergy"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.08.010","article-title":"Decreased expression of type I (IFN-\u03b2) and type III (IFN-\u03bb) interferons and interferon-stimulated genes in patients with chronic rhinosinusitis with and without polyps","volume":"144","author":"Hwang","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/all.12865","article-title":"Relationships between adult asthma and oxidative stress markers and pH in exhaled breath condensate: a systemic review","volume":"71","author":"Aldakheel","year":"2016","journal-title":"Allergy"},{"key":"B21","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1378\/chest.14-2637","article-title":"Oxidative and nitrosative stress and histone deacetylase-2 activity in exacerbations of COPD","volume":"149","author":"Footitt","year":"2016","journal-title":"Chest"},{"key":"B22","doi-asserted-by":"publisher","first-page":"291","DOI":"10.3109\/15412555.2010.496818","article-title":"Current perspectives of oxidative stress and its measurement in chronic obstructive pulmonary disease","volume":"7","author":"Lin","year":"2010","journal-title":"COPD"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1378\/chest.10-2816","article-title":"Hydrogen peroxide in exhaled breath condensate in patients with asthma: A promising biomarker","volume":"140","author":"Teng","year":"2011","journal-title":"Chest"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3109\/15412555.2013.830094","article-title":"Hydrogen peroxide content and pH of expired breath condensate from patients with asthma and COPD","volume":"11","author":"Murata","year":"2014","journal-title":"COPD"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.advenzreg.2006.01.007","article-title":"Nrf2-Keap1 regulation of cellular defense mechanisms against electrophiles and reactive oxygen species","volume":"46","author":"Kobayashi","year":"2006","journal-title":"Adv Enzyme Regul"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2012.06.023","article-title":"Validation of the multiple sensor mechanism of the Keap1-Nrf2 system","volume":"53","author":"Takaya","year":"2012","journal-title":"Free Radic Biol Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b19-00476","article-title":"Impact of gene expression associated with glucocorticoid-induced transcript 1 (GLCCI1) on severe asthma and future exacerbation","volume":"42","author":"Hirai","year":"2019","journal-title":"Biol Pharm Bull"},{"key":"B28","doi-asserted-by":"publisher","first-page":"7090534","DOI":"10.1155\/2019\/7090534","article-title":"Role of Nrf2 and its activator in respiratory diseases","volume":"2019","author":"Liu","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66456-2","article-title":"Effects of n-acetylcysteine on outcomes in chronic obstructive pulmonary disease (bronchitis randomized on NAC cost-utility study, BRONCUS): A randomized placebo controlled trial","volume":"365","author":"Decramer","year":"2005","journal-title":"Lancet"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60869-7","article-title":"Effect of carbocisteine on acute exacerbation of chronic obstructive pulmonary disease (PEACE study): A randomized placebo-controlled study","volume":"371","author":"Zheng","year":"2008","journal-title":"Lancet"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa042976","article-title":"High-dose acetylcysteine in idiopathic pulmonary fibrosis","volume":"353","author":"Demedts","year":"2005","journal-title":"N Engl J Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/alr.21133","article-title":"Expression of dual oxidases and secreted cytokines in chronic rhinosinusitis","volume":"3","author":"Cho","year":"2013","journal-title":"Int Forum Allergy Rhinol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1179\/1351000215Y.0000000001","article-title":"Evaluation of oxidative DNA damage and antioxidant defense in patients with nasal polyps","volume":"20","author":"Mrowicka","year":"2015","journal-title":"Redox Rep"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/S0194-59989770005-6","article-title":"Staging for rhinosinusitis","volume":"117","author":"Lund","year":"1997","journal-title":"Otolaryngol Head Neck Surg"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1067\/mhn.2002.121022","article-title":"Psychometric and clinimetric validity of the 20-item sino-nasal outcome test (SNOT-20)","volume":"126","author":"Piccirillo","year":"2002","journal-title":"Otolaryngol Head Neck Surg"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S0194-59989770001-9","article-title":"Adult rhinosinusitis defined","volume":"117","author":"Lanza","year":"1997","journal-title":"Otolaryngol Head Neck Surg"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2018.1546671","article-title":"Vitamin d status, oxidative stress, and inflammation in children and adolescents: A systematic review","volume":"60","author":"Filgueiras","year":"2020","journal-title":"Crit Rev Food Sci Nutr"},{"key":"B38","doi-asserted-by":"publisher","first-page":"783801","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2002.126780","article-title":"Oxidative stress in allergic respiratory diseases","volume":"110","author":"Bowler","year":"2002","journal-title":"J Allergy Clin Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-061516-045037","article-title":"Oxidative stress","volume":"86","author":"Sies","year":"2017","journal-title":"Annu Rev Biochem"},{"key":"B41","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/B978-0-12-405881-1.00001-X","article-title":"The biological chemistry of hydrogen peroxide","volume":"528","author":"Winterbourn","year":"2013","journal-title":"Methods Enzymol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1177\/147323000903700206","article-title":"The association of oxidative stress and nasal polyposis","volume":"37","author":"Cekin","year":"2009","journal-title":"J Int Med Res"},{"key":"B43","article-title":"Evaluation of total oxidative stress parameters in patients with nasal polyps","volume":"33","author":"Bozkus","year":"2013","journal-title":"Acta Otorhinolaryngol Ital"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2006.01228.x","article-title":"Oxidative stress in nonallergic nasal polyps associated with bronchial hyperresponsiveness","volume":"61","author":"Cheng","year":"2006","journal-title":"Allergy"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200407000-00013","article-title":"Role of free radicals and anti-oxidants in nasal polyps","volume":"114","author":"Dagli","year":"2004","journal-title":"Laryngoscope"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(98)0","article-title":"The role of oxidative stress in rhinovirus-induced elaboration of IL-8 by respiratory epithelial cells","volume":"26","author":"Biagioli","year":"1999","journal-title":"Free Radic Biol Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1080\/1071576021000028316","article-title":"Effect of rhinovirus challenge on antioxidant enzymes in respiratory epithelial cells","volume":"36","author":"Kaul","year":"2002","journal-title":"Free Radic Res"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02765","article-title":"Oxidative stress attenuates TLR3 responsiveness and impairs anti-viral mechanisms in bronchial epithelial cells from COPD and asthma patients","volume":"10","author":"Menzel","year":"2019","journal-title":"Frontier Immunol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(94)90198-8","article-title":"Influenza virus induces expression of antioxidant genes in human epithelial cells","volume":"16","author":"Jacoby","year":"1994","journal-title":"Free Radic Biol Med"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.9089","article-title":"Oxidative stress modulates the expression of toll-like receptors 3 during respiratory syncytial virus infection in human lung epithelial A549 cells","volume":"18","author":"Wang","year":"2018","journal-title":"Mol Med Rep"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0266OC","article-title":"Cigarette smoke decreases innate responses of epithelial cells to rhinovirus infection","volume":"44","author":"Eddleston","year":"2011","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.571003","article-title":"Cigarette smoke affects dendritic cell populations, epithelial barrier function, and the immune response to viral infection with H1N1","volume":"7","author":"Danov","year":"2020","journal-title":"Front Med"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00267.2010","article-title":"Cigarette smoke extracts the RIG-1 initiated innate immune response to influenza virus in the human lung","volume":"300","author":"Wu","year":"2011","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/nature01036","article-title":"Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress","volume":"419","author":"Kops","year":"2002","journal-title":"Nature"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805514200","article-title":"Foxo3a inhibits cardiomyocyte hypertrophy through transactivating catalase","volume":"283","author":"Tan","year":"2008","journal-title":"J Biol Chem"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M710610200","article-title":"FOXO3A regulates peroxiredoxin III expression in human cardiac fibroblasts","volume":"283","author":"Chiribau","year":"2008","journal-title":"J Biol Chem"},{"key":"B57","doi-asserted-by":"publisher","first-page":"18180","DOI":"10.1038\/s41598-019-54567-3","article-title":"FOXO3a regulates rhinovirus-induced innate immune responses in airway epithelial cells","volume":"9","author":"Gimenes-Junior","year":"2019","journal-title":"Sci Rep"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.731968","article-title":"Air pollution exposure impairs airway epithelium IFN-\u03b2 expression in preschool children","volume":"12","author":"Bonato","year":"2021","journal-title":"Front Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.33989\/fimmu.2022.1025796","article-title":"Rhinovirus-induced anti-viral interferon secretion is not deficient and not delayed in sinonasal epithelial cells of patients with chronic rhinosinusitis with nasal polyps","volume":"13","author":"Lee","year":"2022","journal-title":"Front Immunol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1111\/all.13378","article-title":"House dust mite impairs antiviral response in asthma exacerbation models through its effect on TLR3","volume":"73","author":"Akbarshahi","year":"2018","journal-title":"Allergy"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18061112","article-title":"Oxidative stress: promoter of allergic sensitization to protease allergens","volume":"18","author":"van Rijt","year":"2017","journal-title":"Int J Mol Sci"},{"key":"B62","doi-asserted-by":"publisher","first-page":"39","DOI":"10.4049\/jimmunol.1600657","article-title":"Aeroallergens induce reactive oxygen species production and DNA damage and dampen antioxidant responses in bronchial epithelial cells","volume":"199","author":"Chan","year":"2017","journal-title":"J Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0345OC","article-title":"Oxidative stress enhances toll-like receptor 3 response to double-stranded RNA in airway epithelial cells","volume":"42","author":"Koarai","year":"2010","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.tibs.2014.02.002","article-title":"The Nrf2 regulatory network provides an interface between redox and intermediary metabolism","volume":"39","author":"Hayes","year":"2014","journal-title":"Trends Biochem Sci"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2022.102247","article-title":"Regulation of innate immunity by Nrf2","volume":"78","author":"Horst","year":"2022","journal-title":"Curr Opin Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1086381\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T02:19:09Z","timestamp":1676254749000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1086381\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,13]]},"references-count":65,"alternative-id":["10.3389\/fimmu.2023.1086381"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1086381","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.742555315.793598356","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,13]]},"article-number":"1086381"}}