{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T17:56:13Z","timestamp":1791568573731,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T00:00:00Z","timestamp":1645401600000},"content-version":"vor","delay-in-days":51,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Post\u2010infectious bronchiolitis obliterans (PiBO) is a rare, chronic disease initiated by severe infection and followed by perpetuating inflammation and obliteration of the small airways. MicroRNAs (miRNAs) have been proposed to play a central role as epigenetic regulators, which control resolution and prevent the uncontrolled progress of inflammation. The aim of this study was to define biomarkers on the level of post\u2010transcriptional gene regulation in order to characterise PiBO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 39 patients with well\u2010defined PiBO and 31 controls from two centres, Barcelona, Spain, and Frankfurt, Germany, were analysed by next\u2010generation sequencing (NGS). The evaluation of the biological targets of the miRNAs was performed by pathway enrichment analysis and protein\u2013protein interaction network analysis respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with PiBO had significantly lower lung function values and increased airway inflammation in induced sputum as indicated by total cell counts, neutrophils, IL\u20101\u03b2, IL\u20106, IL\u20108 and TGF\u2010\u03b2 compared to controls.<\/jats:p><jats:p>Next\u2010generation sequencing analysis revealed a total of 22 dysregulated miRNAs, which passed significance threshold for <jats:italic>P<\/jats:italic>adj \u2264\u20090.001 with 17 being upregulated and 5 being downregulated. Of these dysregulated miRNAs, miR\u2010335\u20105p, miR\u2010186\u20105p, miR\u201030b\u20105p and miR\u201030c\u20105p were further validated using qRT\u2010PCR. Interestingly, these miRNAs are functionally implicated in cytokine\u2013cytokine receptor interaction, TGF\u2010\u03b2 signalling and FoxO signalling pathway and significantly correlated with lung function values (FEV1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrate an aberrant miRNA expression profile in PiBO, which impacts pathways responsible for the regulation of inflammation and fibrosis. The defined miRNAs are useful biomarkers and should be assessed as potential target in the field of miRNA therapeutics.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1376","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T10:24:36Z","timestamp":1645439076000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Epigenetic regulation of inflammation by microRNAs in post\u2010infectious bronchiolitis obliterans"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1292-648X","authenticated-orcid":false,"given":"Ruth P","family":"Duecker","sequence":"first","affiliation":[{"name":"Division for Allergy, Pneumology and Cystic Fibrosis Department for Children and Adolescence Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"De Mir Messa","sequence":"additional","affiliation":[{"name":"Allergy, Pulmonology and Cystic Fibrosis Section Department of Pediatrics Vall d\u2019Hebron Hospital Universitari Universitat Aut\u00f2noma de Barcelona Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvija\u2010Pera","family":"Jerkic","sequence":"additional","affiliation":[{"name":"Division for Allergy, Pneumology and Cystic Fibrosis Department for Children and Adolescence Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalena","family":"Kochems","sequence":"additional","affiliation":[{"name":"Division for Allergy, Pneumology and Cystic Fibrosis Department for Children and Adolescence Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Gottwald","sequence":"additional","affiliation":[{"name":"Division for Allergy, Pneumology and Cystic Fibrosis Department for Children and Adolescence Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Moreno\u2010Gald\u00f3","sequence":"additional","affiliation":[{"name":"Allergy, Pulmonology and Cystic Fibrosis Section Department of Pediatrics Vall d\u2019Hebron Hospital Universitari Universitat Aut\u00f2noma de Barcelona Barcelona Spain"},{"name":"CIBER of Rare Diseases (CIBERER) Instituto de Salud Carlos III (ISCIII) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Rosewich","sequence":"additional","affiliation":[{"name":"Division for Allergy, Pneumology and Cystic Fibrosis Department for Children and Adolescence Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Gronau","sequence":"additional","affiliation":[{"name":"Division for Allergy, Pneumology and Cystic Fibrosis Department for Children and Adolescence Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Zielen","sequence":"additional","affiliation":[{"name":"Division for Allergy, Pneumology and Cystic Fibrosis Department for Children and Adolescence Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Geburtig\u2010Chiocchetti","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Kreyenberg","sequence":"additional","affiliation":[{"name":"Division for Stem Cell Transplantation and Immunology Department for Children and Adolescence Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Schubert","sequence":"additional","affiliation":[{"name":"Division for Allergy, Pneumology and Cystic Fibrosis Department for Children and Adolescence Goethe University Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20145"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.24221"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.20784"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2014.10.026"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2005.052670"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-016-9907-y"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-013-8398-3"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09267"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1672-0229(08)60044-3"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.09.015"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00298"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2017-0249"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/4641585"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2014-205328"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5852827"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200007270-00022"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2021.12446"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20205176"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2020.109596"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-019-1184-x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10060945"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2019.04.007"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5390107"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.13415"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/14728222.2018.1406922"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjresp-2016-000177"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2020.105944"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3345\/kjp.2015.58.12.459"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5170"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022236"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-010-0949-x"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.911398"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.169"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0185619"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13548"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2009.10.013"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02530"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms151018000"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2018.09.009"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/834805"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.816595"},{"key":"e_1_2_8_43_1","first-page":"320","article-title":"Lentiviral vector\u2010mediated delivery of lysophosphatidylcholine acyltransferase 1 attenuates airway inflammation in ovalbumin\u2010induced allergic asthmatic mice","volume":"33","author":"Cheng S","year":"2015","journal-title":"Asian Pac J Allergy Immunol"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2017.04.002"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000001595"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.24801"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-018-0683-8"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2010.02.004"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2019.106378"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv403"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1376","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cti2.1376","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1376","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T15:18:21Z","timestamp":1693149501000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.1376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1002\/cti2.1376"],"URL":"https:\/\/doi.org\/10.1002\/cti2.1376","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"value":"2050-0068","type":"print"},{"value":"2050-0068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]},"assertion":[{"value":"2021-03-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1376"}}