{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T02:44:28Z","timestamp":1761965068677,"version":"3.37.3"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T00:00:00Z","timestamp":1548720000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T00:00:00Z","timestamp":1548720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T00:00:00Z","timestamp":1548720000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature and Science Foundation of China","doi-asserted-by":"crossref","award":["81870706","31570932","81700888","81701589"],"award-info":[{"award-number":["81870706","31570932","81700888","81701589"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003453","name":"Guangdong Nature Science Foundation","doi-asserted-by":"crossref","award":["2015A030313786"],"award-info":[{"award-number":["2015A030313786"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Nature and Science Foundation of China","doi-asserted-by":"crossref","award":["81870706","31570932","81700888","81701589"],"award-info":[{"award-number":["81870706","31570932","81700888","81701589"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003453","name":"Guangdong Nature Science Foundation","doi-asserted-by":"crossref","award":["2015A030313786"],"award-info":[{"award-number":["2015A030313786"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,3,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>T helper (Th)2 polarization plays an important role in the pathogenesis of allergic diseases; the underlying mechanism remains to be further investigated. B cell lymphoma protein-2 like protein-12 (Bcl2L12) has the anti-apoptotic function. This study aims to elucidate the contribution of Bcl2L12 to Th2 polarization in patients with allergic rhinitis (AR). In this study, human CD4+ T cells were isolated from blood samples collected from AR patients and healthy control (HC) subjects. The immune response profiles of CD4+ T cells were analyzed by immunologic approaches. The results showed that AR CD4+ T cells (CD4+ T cells collected from AR patients) showed defects of apoptosis. The expression of FasL in AR CD4+ T cells was lower than that of HC CD4+ T cells. Serum IL-5 levels were negatively correlated with the expression of FasL in AR CD4+ T cells. Exposure of CD4+ T cells to IL-5 in the culture suppressed the expression of FasL and increased the expression of Bcl2L12. IL-5 increased the levels of Bcl2L12 in CD4+ T cells, the latter bound to the FasL promoter to prevent FasL gene transcription. Inhibition of Bcl2L12 restored the apoptosis machinery in AR CD4+ T cells. In conclusion, overexpression of Bcl2L12 in CD4+ T cells compromises the apoptosis machinery; the latter can be restored by inhibition of Bcl2L12. BcL2L12 in CD4+ T cells may be a novel target for the treatment of AR and other allergic disorders.<\/jats:p>","DOI":"10.1002\/jlb.3a0718-287rr","type":"journal-article","created":{"date-parts":[[2019,1,29]],"date-time":"2019-01-29T23:47:46Z","timestamp":1548805666000},"page":"719-727","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Interleukin-5 induces apoptotic defects in CD4+ T cells of patients with allergic rhinitis"],"prefix":"10.1093","volume":"105","author":[{"given":"Xiang-Qian","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Pediatric Otolaryngology, Southern Medical University , Shenzhen, China"},{"name":"Department of Otolaryngology, Guangzhou Medical University , Guangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, First Affiliated Hospital of Guangzhou Medical University , Guangzhou, China"},{"name":"Research Center of Allergy & Immunology, Shenzhen University School of Medicine , Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center of Allergy & Immunology, Shenzhen University School of Medicine , Shenzhen, China"},{"name":"Longgang ENT Hospital & Shenzhen ENT Institute , Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Zhen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Research Center of Allergy & Immunology, Shenzhen University School of Medicine , Shenzhen, China"},{"name":"Longgang ENT Hospital & Shenzhen ENT Institute , Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Bo","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Beijing Pediatric Hospital , Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Rui","family":"Geng","sequence":"additional","affiliation":[{"name":"Research Center of Allergy & Immunology, Shenzhen University School of Medicine , Shenzhen, China"},{"name":"Longgang ENT Hospital & Shenzhen ENT Institute , Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang-Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Research Center of Allergy & Immunology, Shenzhen University School of Medicine , Shenzhen, China"},{"name":"Longgang ENT Hospital & Shenzhen ENT Institute , Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Hua","family":"Mo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Otolaryngology, Southern Medical University , Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Allergy, Third Affiliated Hospital of Shenzhen University , Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Gang","family":"Liu","sequence":"additional","affiliation":[{"name":"Research Center of Allergy & Immunology, Shenzhen University School of Medicine , Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da-Bo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Otolaryngology, Southern Medical University , Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping-Chang","family":"Yang","sequence":"additional","affiliation":[{"name":"Research Center of Allergy & Immunology, Shenzhen University School of Medicine , Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,1,29]]},"reference":[{"key":"2023032406175257800_jlb10316-cit-0001","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/j.1600-065X.2011.01034.x","article-title":"Immune modulation for treatment of allergic disease?","volume":"242","author":"Nguyen","year":"2011","journal-title":"Immunol Rev"},{"key":"2023032406175257800_jlb10316-cit-0002","first-page":"222","article-title":"Effect of allergic rhinitis and asthma on the quality of life in young Thai adolescents?","volume":"33","author":"Sritipsukho","year":"2015","journal-title":"Asian Pac J Allergy Immunol"},{"key":"2023032406175257800_jlb10316-cit-0003","doi-asserted-by":"crossref","first-page":"187","DOI":"10.2500\/ajra.2012.26.3762","article-title":"The united allergic airway: connections between allergic rhinitis, asthma, and chronic sinusitis?","volume":"26","author":"Feng","year":"2012","journal-title":"Am J Rhinol Allergy"},{"key":"2023032406175257800_jlb10316-cit-0004","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1159\/000358505","article-title":"Allergic rhinitis?","volume":"100","author":"Mygind","year":"2014","journal-title":"Chem Immunol Allergy"},{"key":"2023032406175257800_jlb10316-cit-0005","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1111\/all.12090","article-title":"Aberrant dendritic cell function conditions Th2-cell polarization in allergic rhinitis?","volume":"68","author":"Pilette","year":"2013","journal-title":"Allergy"},{"key":"2023032406175257800_jlb10316-cit-0006","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1586\/1744666X.2015.1086645","article-title":"From IgE to clinical trials of allergic rhinitis?","volume":"11","author":"Ciprandi","year":"2015","journal-title":"Expert Rev Clin Immunol"},{"key":"2023032406175257800_jlb10316-cit-0007","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1002\/alr.21381","article-title":"Pharmacotherapy for allergic rhinitis?","volume":"2","author":"Platt","year":"2014","journal-title":"Int Forum Allergy Rhinol 4 Suppl"},{"key":"2023032406175257800_jlb10316-cit-0008","first-page":"223","article-title":"Th1\/Th2 balance: the hypothesis, its limitations, and implications for health and disease?","volume":"8","author":"Kidd","year":"2003","journal-title":"Altern Med Rev"},{"key":"2023032406175257800_jlb10316-cit-0009","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3410\/B4-6","article-title":"Cellular networks controlling Th2 polarization in allergy and immunity?","volume":"4","author":"Kool","year":"2012","journal-title":"F1000 Biol Rep"},{"key":"2023032406175257800_jlb10316-cit-0010","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1615\/CritRevImmunol.2014009988","article-title":"Mechanism of activation-induced cell death of T cells and regulation of FasL expression?","volume":"34","author":"Arakaki","year":"2014","journal-title":"Crit Rev Immunol"},{"key":"2023032406175257800_jlb10316-cit-0011","first-page":"75","article-title":"Enhanced proliferation and defective activation-induced cell death of CD4+ T cells in childhood asthma?","volume":"32","author":"Jiang","year":"2014","journal-title":"Asian Pac J Allergy Immunol"},{"key":"2023032406175257800_jlb10316-cit-0012","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1111\/all.13186","article-title":"Protease-activated receptor-2 suppresses interleukin (IL)-10 expression in B cells via upregulating Bcl2L12 in patients with allergic rhinitis?","volume":"72","author":"Xue","year":"2017","journal-title":"Allergy"},{"key":"2023032406175257800_jlb10316-cit-0013","doi-asserted-by":"crossref","first-page":"725","DOI":"10.4049\/jimmunol.1800139","article-title":"Bcl2L12 contributes to Th2-biased inflammation in the intestinal mucosa by regulating CD4(+) T cell activities?","volume":"201","author":"Li","year":"2018","journal-title":"J Immunol"},{"key":"2023032406175257800_jlb10316-cit-0014","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/cbf.3250","article-title":"Tumor necrosis factor suppresses interleukin 10 in peripheral B cells via upregulating Bcl2-like protein 12 in patients with inflammatory bowel disease?","volume":"35","author":"Guo","year":"2017","journal-title":"Cell Biochem Funct"},{"key":"2023032406175257800_jlb10316-cit-0015","doi-asserted-by":"crossref","first-page":"33","DOI":"10.4161\/cc.10.1.14365","article-title":"Beyond effector caspase inhibition: bcl2L12 neutralizes p53 signaling in glioblastoma?","volume":"10","author":"Stegh","year":"2011","journal-title":"Cell Cycle"},{"key":"2023032406175257800_jlb10316-cit-0016","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1385\/MB:25:1:19","article-title":"The Fas\/Fas ligand system and cancer: immune privilege and apoptosis?","volume":"25","author":"Abrahams","year":"2003","journal-title":"Mol Biotechnol"},{"key":"2023032406175257800_jlb10316-cit-0017","first-page":"905","article-title":"GSK3betamediated Ser156 phosphorylation modulates a BH3like domain in BCL2L12 during TMZinduced apoptosis and autophagy in glioma cells?","volume":"42","author":"Chu","year":"2018","journal-title":"Int J Mol Med"},{"key":"2023032406175257800_jlb10316-cit-0018","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1038\/sj.onc.1205231","article-title":"Deregulated c-Myc prematurely recruits both Type I and II CD95\/Fas apoptotic pathways associated with terminal myeloid differentiation?","volume":"21","author":"Amanullah","year":"2002","journal-title":"Oncogene"},{"key":"2023032406175257800_jlb10316-cit-0019","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1034\/j.1600-065X.2003.00051.x","article-title":"Activation-induced cell death in T cells?","volume":"193","author":"Green","year":"2003","journal-title":"Immunol Rev"},{"key":"2023032406175257800_jlb10316-cit-0020","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.clinbiochem.2014.09.008","article-title":"BCL2L12: a promising molecular prognostic biomarker in breast cancer?","volume":"47","author":"Tzovaras","year":"2014","journal-title":"Clin Biochem"},{"key":"2023032406175257800_jlb10316-cit-0021","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1111\/j.1365-2222.2011.03854.x","article-title":"Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor?","volume":"42","author":"Molfino","year":"2012","journal-title":"Clin Exp Allergy"},{"key":"2023032406175257800_jlb10316-cit-0022","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1016\/j.jaci.2012.02.032","article-title":"Local allergic rhinitis: concept, pathophysiology, and management?","volume":"129","author":"Rondon","year":"2012","journal-title":"J Allergy Clin Immunol"}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2FJLB.3A0718-287RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/JLB.3A0718-287RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/JLB.3A0718-287RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/105\/4\/719\/49484658\/jlb10316.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/105\/4\/719\/49484658\/jlb10316.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T06:26:59Z","timestamp":1679639219000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/105\/4\/719\/6935762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,29]]},"references-count":22,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,1,29]]},"published-print":{"date-parts":[[2019,3,22]]}},"URL":"https:\/\/doi.org\/10.1002\/jlb.3a0718-287rr","relation":{},"ISSN":["1938-3673","0741-5400"],"issn-type":[{"type":"electronic","value":"1938-3673"},{"type":"print","value":"0741-5400"}],"subject":[],"published-other":{"date-parts":[[2019,4]]},"published":{"date-parts":[[2019,1,29]]},"assertion":[{"value":"2018-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}