{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T20:36:44Z","timestamp":1777581404604,"version":"3.51.4"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"10-11","license":[{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:00:00Z","timestamp":1659484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Changsha Natural Science Foundation","award":["kq2007071"],"award-info":[{"award-number":["kq2007071"]}]},{"name":"Hunan Natural Science Foundation in China","award":["2021JJ40933"],"award-info":[{"award-number":["2021JJ40933"]}]},{"name":"Hunan Natural Science Foundation in China","award":["2017SK2043"],"award-info":[{"award-number":["2017SK2043"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870708"],"award-info":[{"award-number":["81870708"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Inflamm. Res."],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background and objectives<\/jats:title>\n                <jats:p>miRNAs play a crucial role in regulating immune responses. However, the effect of miR-124-3p on type 2 inflammation in allergic rhinitis (AR) is unclear. We aimed to study the immune regulation of miR-124-3p in AR and the mechanisms involved.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The direct interaction\u00a0between\u00a0miR-124-3p and IL-4R\u03b1 was confirmed through a dual-luciferase reporter assay. In vitro splenic lymphocytes from mice and peripheral blood mononuclear cells (PBMCs) from healthy individuals were cultured and treated with miR-124-3p mimic\/inhibitor. Twenty-four female C57BL\/C mice were divided into four groups: control, AR model, miR-124-3p agomir, and miR-124-3p antagomir groups (<jats:italic>n<\/jats:italic>\u2009=\u20096 per\u00a0group). The allergic responses were evaluated based on the number of sneezing and nasal scratching, the serum\u00a0HDM-specific IgE (sIgE)\u00a0levels, and the degree of nasal mucosa eosinophil infiltration. The expression of IL-4R\u03b1, p-STAT6, and type 2 inflammatory cytokines (IL-4, IL-5 and IL-13) in lymphocytes or nasal mucosa was determined by qPCR, western blotting, flow cytometry, immunohistochemistry and immunofluorescence.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>miR-124-3p directly targets the 3'UTR of IL-4R\u03b1. The miR-124-3p mimic lowered the IL-4R\u03b1, p-STAT6, IL-4, IL-5, and IL-13 expression levels in both mouse splenic lymphocytes and human PBMCs in vitro, and the miR-124-3p inhibitor rescued these changes. Furthermore, the miR-124-3p agomir decreased the levels of IL-4R\u03b1 and IL-4 in nasal mucosa, Th2 differentiation in spleen, and allergic response in AR mice. Moreover, the miR-124-3p antagonist increased the IL-4R\u03b1 and IL-4 levels and further aggravated the allergic responses.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>miR-124-3p might attenuate type 2 inflammation in AR by regulating IL-4R\u03b1 signaling, and miR-124-3p may be a promising new target in AR treatment.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00011-022-01614-x","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T19:07:46Z","timestamp":1659553666000},"page":"1271-1282","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Increased miR-124-3p alleviates type 2 inflammatory response in allergic rhinitis via IL-4R\u03b1"],"prefix":"10.1007","volume":"71","author":[{"given":"Qian","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifang","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Chu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiansheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honghui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guolin","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,8,3]]},"reference":[{"key":"1614_CR1","doi-asserted-by":"publisher","first-page":"300","DOI":"10.4168\/aair.2018.10.4.300","volume":"10","author":"L Cheng","year":"2018","unstructured":"Cheng L, Chen J, Fu Q, et al. Chinese society of allergy guidelines for diagnosis and treatment of allergic rhinitis. Allergy Asthma Immunol Res. 2018;10:300\u201353.","journal-title":"Allergy Asthma Immunol Res"},{"key":"1614_CR2","first-page":"147","volume":"24","author":"RA Settipane","year":"2003","unstructured":"Settipane RA. Rhinitis: a dose of epidemiological reality. Allergy Asthma Proc. 2003;24:147\u201354.","journal-title":"Allergy Asthma Proc"},{"key":"1614_CR3","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1177\/0194599814561600","volume":"152","author":"MD Seidman","year":"2015","unstructured":"Seidman MD, Gurgel RK, Lin SY, et al. Clinical practice guideline: allergic rhinitis. Otolaryngol Head Neck Surg. 2015;152:S1\u201343.","journal-title":"Otolaryngol Head Neck Surg"},{"key":"1614_CR4","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1016\/j.jaci.2017.03.050","volume":"140","author":"JL Brozek","year":"2017","unstructured":"Brozek JL, Bousquet J, Agache I, et al. Allergic rhinitis and its impact on asthma (ARIA) guidelines-2016 revision. J Allergy Clin Immunol. 2017;140:950\u20138.","journal-title":"J Allergy Clin Immunol"},{"key":"1614_CR5","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.cell.2009.01.002","volume":"136","author":"DP Bartel","year":"2009","unstructured":"Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215\u201333.","journal-title":"Cell"},{"key":"1614_CR6","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/j.cell.2009.01.035","volume":"136","author":"RW Carthew","year":"2009","unstructured":"Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell. 2009;136:642\u201355.","journal-title":"Cell"},{"issue":"6","key":"1614_CR7","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1111\/all.14646","volume":"76","author":"J Weidner","year":"2021","unstructured":"Weidner J, Bartel S, Kilic A, et al. Spotlight on microRNAs in allergy and asthma. Allergy. 2021;76(6):1661\u201378.","journal-title":"Allergy"},{"key":"1614_CR8","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1016\/j.jaci.2016.01.029","volume":"137","author":"RP Panganiban","year":"2016","unstructured":"Panganiban RP, Wang Y, Howrylak J, et al. Circulating microRNAs as biomarkers in patients with allergic rhinitis and asthma. J Allergy Clin Immunol. 2016;137:1423\u201332.","journal-title":"J Allergy Clin Immunol"},{"key":"1614_CR9","doi-asserted-by":"publisher","first-page":"6558","DOI":"10.3892\/mmr.2017.7411","volume":"16","author":"M Hou","year":"2017","unstructured":"Hou M, Li W, Xie Z, Ai J, Sun B, Tan G. Effects of anticholinergic agent on miRNA profiles and transcriptomes in a murine model of allergic rhinitis. Mol Med Rep. 2017;16:6558\u201369.","journal-title":"Mol Med Rep"},{"key":"1614_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.108279","volume":"101","author":"S Zhang","year":"2021","unstructured":"Zhang S, Dong D, Zhang Y, Wang J, Liu L, Zhao Y. miR-124-3p relieves allergic rhinitis by inhibiting dipeptidyl peptidase-4. Int Immunopharmacol. 2021;101: 108279.","journal-title":"Int Immunopharmacol"},{"key":"1614_CR11","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1177\/0194599820965233","volume":"164","author":"CC Damask","year":"2021","unstructured":"Damask CC, Ryan MW, Casale TB, et al. Targeted molecular therapies in allergy and rhinology. Otolaryngol Head Neck Surg. 2021;164:S1\u201321.","journal-title":"Otolaryngol Head Neck Surg"},{"key":"1614_CR12","doi-asserted-by":"crossref","unstructured":"Liang Y, Xie J, Che D, et al. MiR-124-3p helps to protect against acute respiratory distress syndrome by targeting p65. Biosci Rep. 2020;40:BSR20192132.","DOI":"10.1042\/BSR20192132"},{"key":"1614_CR13","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/S0960-9822(02)00809-6","volume":"12","author":"M Lagos-Quintana","year":"2002","unstructured":"Lagos-Quintana M, Rauhut R, Yalcin A, et al. Identification of tissue-specific microRNAs from mouse. Curr Biol. 2002;12:735\u20139.","journal-title":"Curr Biol"},{"key":"1614_CR14","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.stem.2009.04.007","volume":"4","author":"T Papagiannakopoulos","year":"2009","unstructured":"Papagiannakopoulos T, Kosik KS. MicroRNA-124: micromanager of neurogenesis. Cell Stem Cell. 2009;4:375\u20136.","journal-title":"Cell Stem Cell"},{"key":"1614_CR15","doi-asserted-by":"publisher","first-page":"871","DOI":"10.3892\/ijo.2014.2756","volume":"46","author":"K Smerkova","year":"2015","unstructured":"Smerkova K, Hudcova K, Vlahova V, et al. Label-free and amplification-free miR-124 detection in human cells. Int J Oncol. 2015;46:871\u20137.","journal-title":"Int J Oncol"},{"key":"1614_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2021.104284","volume":"362","author":"J Chen","year":"2021","unstructured":"Chen J, Peng L, Zhao Z, et al. HDAC1 potentiates CD4 + T cell activation by inhibiting miR-124 and promoting IRF1 in systemic lupus erythematosus. Cell Immunol. 2021;362: 104284.","journal-title":"Cell Immunol"},{"key":"1614_CR17","doi-asserted-by":"publisher","first-page":"25414","DOI":"10.1074\/jbc.M113.460287","volume":"288","author":"K Kang","year":"2013","unstructured":"Kang K, Peng X, Zhang X, et al. MicroRNA-124 suppresses the transactivation of nuclear factor of activated T cells by targeting multiple genes and inhibits the proliferation of pulmonary artery smooth muscle cells. J Biol Chem. 2013;288:25414\u201327.","journal-title":"J Biol Chem"},{"key":"1614_CR18","first-page":"7676813","volume":"12","author":"P Li","year":"2021","unstructured":"Li P, Wang L, He J, et al. MicroRNA-124 Promotes Singapore grouper iridovirus replication and negatively regulates innate immune response. Front Immunol. 2021;12:7676813.","journal-title":"Front Immunol"},{"key":"1614_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.108540","volume":"105","author":"Q Zhou","year":"2022","unstructured":"Zhou Q, He D, Deng Y, et al. MiR-124-3p targeting PDE4B attenuates LPS-induced ALI through the TLR4\/NF-\u03baB signaling pathway. Int Immunopharmacol. 2022;105: 108540.","journal-title":"Int Immunopharmacol"},{"key":"1614_CR20","doi-asserted-by":"publisher","first-page":"11596","DOI":"10.1038\/ncomms11596","volume":"7","author":"Z Chen","year":"2016","unstructured":"Chen Z, Andreev D, Oeser K, et al. Th2 and eosinophil responses suppress inflammatory arthritis. Nat Commun. 2016;7:11596.","journal-title":"Nat Commun"},{"key":"1614_CR21","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1038\/ni.1656","volume":"9","author":"W Liao","year":"2008","unstructured":"Liao W, Schones DE, Oh J, et al. Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor alpha-chain expression. Nat Immunol. 2008;9:1288\u201396.","journal-title":"Nat Immunol"},{"key":"1614_CR22","doi-asserted-by":"publisher","first-page":"7276","DOI":"10.4049\/jimmunol.166.12.7276","volume":"166","author":"J Zhu","year":"2001","unstructured":"Zhu J, Guo L, Watson CJ, Hu-Li J, Paul WE. Stat6 is necessary and sufficient for IL-4\u2019s role in Th2 differentiation and cell expansion. J Immunol. 2001;166:7276\u201381.","journal-title":"J Immunol"},{"key":"1614_CR23","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1038\/cr.2013.116","volume":"23","author":"Y Sun","year":"2013","unstructured":"Sun Y, Li Q, Gui H, et al. MicroRNA-124 mediates the cholinergic anti-inflammatory action through inhibiting the production of pro-inflammatory cytokines. Cell Res. 2013;23:1270\u201383.","journal-title":"Cell Res"},{"key":"1614_CR24","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1096\/fj.201700673r","volume":"32","author":"S Huang","year":"2018","unstructured":"Huang S, Ge X, Yu J, et al. Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons. FASEB J. 2018;32:512\u201328.","journal-title":"FASEB J"},{"issue":"9","key":"1614_CR25","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.clinbiochem.2016.02.016","volume":"49","author":"TH Rainer","year":"2016","unstructured":"Rainer TH, Leung LY, Chan CPY, et al. Plasma miR-124-3p and miR-16 concentrations as prognostic markers in acute stroke. Clin Biochem. 2016;49(9):663\u20138.","journal-title":"Clin Biochem"},{"key":"1614_CR26","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.2147\/JAA.S331090","volume":"14","author":"J Zhang","year":"2021","unstructured":"Zhang J, Wang Z, Zhang D, et al. Integrative analysis reveals a miRNA-mRNA regulatory network and potential causative agents in the asthmatic airway epithelium. J Asthma Allergy. 2021;14:1307\u201321.","journal-title":"J Asthma Allergy"}],"container-title":["Inflammation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00011-022-01614-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00011-022-01614-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00011-022-01614-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T04:20:07Z","timestamp":1666930807000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00011-022-01614-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,3]]},"references-count":26,"journal-issue":{"issue":"10-11","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["1614"],"URL":"https:\/\/doi.org\/10.1007\/s00011-022-01614-x","relation":{},"ISSN":["1023-3830","1420-908X"],"issn-type":[{"value":"1023-3830","type":"print"},{"value":"1420-908X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,3]]},"assertion":[{"value":"28 March 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}