{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:30:34Z","timestamp":1792531834039,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Respiratory J"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Idiopathic pulmonary fibrosis (IPF) leads to irreversible scarring of lung tissue, resulting in deteriorating respiratory function, particularly in older adults. We aimed to explore the causative link between hypothyroidism and IPF, particularly focusing on immune cell phenotypes as mediating factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A two\u2010sample Mendelian randomization (MR) approach was utilized to investigate the influence of hypothyroidism on IPF and the role of 731 distinct immune cell phenotypes as mediators. The mediating effects were quantified using the coefficient product method. Various sensitivity analyses, including Cochran's <jats:italic>Q<\/jats:italic> test for heterogeneity, MR\u2013Egger for pleiotropy, and the \u201cleave\u2010one\u2010out\u201d method, were conducted to verify the robustness of single\u2010nucleotide polymorphism\u2013derived casual estimates. Statistical analyses were carried out using the R software (Version 4.3.1).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hypothyroidism was significantly associated with increased IPF risk (odds ratio [OR]\u2009=\u20091.13, 95% confidence interval [CI]\u2009=\u20091.06\u20131.21, <jats:italic>p<\/jats:italic>\u2009=\u20091.34\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>). Of the 36 immune cell phenotypes associated with IPF, those related to the mean fluorescence intensity of B cells were the most prevalent. Mediation analysis showed that CD19 on IgD\u2212 CD27\u2212 accounted for approximately 3.68% of the effect of hypothyroidism on IPF, whereas herpesvirus entry mediator (HVEM) on T cells accounted for approximately 3.83% of this effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identified a marked association between hypothyroidism and IPF. Specific immune cell phenotypes may partially mediate this relationship, although the observed effect sizes were modest. Further research is needed to validate these results in diverse populations and larger clinical trials.<\/jats:p><\/jats:sec>","DOI":"10.1111\/crj.70111","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T08:08:47Z","timestamp":1752134927000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Role of Immune Cells in Mediating the Effect of Hypothyroidism on Idiopathic Pulmonary Fibrosis"],"prefix":"10.1111","volume":"19","author":[{"given":"Zhengling","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Department Gansu Province Central Hospital &amp; Gansu Provincial Maternity and Child Care Hospital  Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4301-4237","authenticated-orcid":false,"given":"Chengkun","family":"Kou","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical School, Lanzhou University  Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Department Gansu Province Central Hospital &amp; Gansu Provincial Maternity and Child Care Hospital  Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Department Gansu Province Central Hospital &amp; Gansu Provincial Maternity and Child Care Hospital  Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Department Gansu Province Central Hospital &amp; Gansu Provincial Maternity and Child Care Hospital  Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongning","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Department Gansu Province Central Hospital &amp; Gansu Provincial Maternity and Child Care Hospital  Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Department Gansu Province Central Hospital &amp; Gansu Provincial Maternity and Child Care Hospital  Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Department Gansu Province Central Hospital &amp; Gansu Provincial Maternity and Child Care Hospital  Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9584-222X","authenticated-orcid":false,"given":"Liang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Department Gansu Province Central Hospital &amp; Gansu Provincial Maternity and Child Care Hospital  Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.3669"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2024.100729"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202202-0399ST"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-2714"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0572"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2017.00123"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2023.02.038"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2014.10.016"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1378969"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000097133"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI143226"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrtlng.2024.06.003"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-024-02942-w"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.17219"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a038984"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyu176"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1360851"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-0684-4"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1408770"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyq151"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103592"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.15555.3"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1705751"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103669"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74942"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4447"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2023-0080OC"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1379480"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-024-01345-9"}],"container-title":["The Clinical Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/crj.70111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,27]],"date-time":"2025-07-27T23:33:11Z","timestamp":1753659191000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/crj.70111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":30,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1111\/crj.70111"],"URL":"https:\/\/doi.org\/10.1111\/crj.70111","archive":["Portico"],"relation":{},"ISSN":["1752-6981","1752-699X"],"issn-type":[{"value":"1752-6981","type":"print"},{"value":"1752-699X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"2024-12-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70111"}}