{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T05:40:16Z","timestamp":1792302016316,"version":"4.4.0"},"reference-count":44,"publisher":"Wiley","issue":"45","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"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 Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32360184"],"award-info":[{"award-number":["32360184"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32100710"],"award-info":[{"award-number":["32100710"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Progranulin (PGRN) plays a critical role in bronchial asthma and the function of various immune cells. However, the mechanisms by which PGRN influences B\u2010cell receptor (BCR) signaling and immunoglobulin E(IgE) production are not fully understood. The study aimed to elucidate the molecular mechanisms through which PGRN affects BCR signaling, B\u2010cell differentiation, and IgE production. A PGRN knockout mouse model, along with techniques including flow cytometry, the creation of a bone marrow chimeric mouse model, total internal reflection fluorescence (TIRF), and Western blot (WB) analysis is employed, to investigate the link between PGRN and various aspects of B\u2010cell biology. It is discovered that the absence of PGRN in mice alters peripheral B\u2010cell subpopulations, promotes IgE class switching in a cell\u2010intrinsic manner, and affects B\u2010cell subpopulations. Additionally, PGRN modulates B\u2010cell functions by regulating BCR signaling pathways, metabolic processes, and the actin cytoskeleton during early B\u2010cell activation. Significantly, PGRN deficiency results in diminished production of NP\u2010specific antibodies. Moreover, it is found that PGRN inhibits B\u2010cell activation and IgE production through the PGRN\u2010IFITM3\u2010STAT1 signaling pathway. The findings provide new strategies for the targeted treatment of bronchial asthma, highlighting the crucial role of PGRN in B\u2010cell signaling and IgE production.<\/jats:p>","DOI":"10.1002\/advs.202403939","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T07:09:31Z","timestamp":1729062571000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["PGRN Inhibits Early B\u2010cell Activation and IgE Production Through the IFITM3\u2010STAT1 Signaling Pathway in Asthma"],"prefix":"10.1002","volume":"11","author":[{"given":"Pingping","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Zunyi Medical University  Zunyi 563000 China"},{"name":"Department of Pediatrics Guizhou Children's Hospital  Zunyi 563000 China"},{"name":"Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University  Zunyi 563099 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changshun","family":"Ruan","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Child Infection and Immunity Children's Hospital of Chongqing Medical University  Chongqing 400014 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangli","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Zunyi Medical University  Zunyi 563000 China"},{"name":"Department of Pediatrics Guizhou Children's Hospital  Zunyi 563000 China"},{"name":"Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University  Zunyi 563099 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaning","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Zunyi Medical University  Zunyi 563000 China"},{"name":"Department of Pediatrics Guizhou Children's Hospital  Zunyi 563000 China"},{"name":"Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University  Zunyi 563099 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Zunyi Medical University  Zunyi 563000 China"},{"name":"Department of Pediatrics Guizhou Children's Hospital  Zunyi 563000 China"},{"name":"Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University  Zunyi 563099 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Zunyi Medical University  Zunyi 563000 China"},{"name":"Department of Pediatrics Guizhou Children's Hospital  Zunyi 563000 China"},{"name":"Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University  Zunyi 563099 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Dai","sequence":"additional","affiliation":[{"name":"Zhanjiang Institute of Clinical Medicine Zhanjiang Central Hospital Guangdong Medical University  Zhanjiang 524037 China"},{"name":"Department of Hematology Central People's Hospital of Zhanjiang  Zhanjiang 524037 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"An","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Zunyi Medical University  Zunyi 563000 China"},{"name":"Department of Pediatrics Guizhou Children's Hospital  Zunyi 563000 China"},{"name":"Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University  Zunyi 563099 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Zunyi Medical University  Zunyi 563000 China"},{"name":"Department of Pediatrics Guizhou Children's Hospital  Zunyi 563000 China"},{"name":"Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University  Zunyi 563099 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Zunyi Medical University  Zunyi 563000 China"},{"name":"Department of Pediatrics Guizhou Children's Hospital  Zunyi 563000 China"},{"name":"Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University  Zunyi 563099 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Zunyi Medical University  Zunyi 563000 China"},{"name":"Department of Pediatrics Guizhou Children's Hospital  Zunyi 563000 China"},{"name":"Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University  Zunyi 563099 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixu","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Zunyi Medical University  Zunyi 563000 China"},{"name":"Department of Pediatrics Guizhou Children's Hospital  Zunyi 563000 China"},{"name":"Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University  Zunyi 563099 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuochen","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Affiliated Hospital of Zunyi Medical University  Zunyi 563000 China"},{"name":"Department of Pediatrics Guizhou Children's Hospital  Zunyi 563000 China"},{"name":"Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University  Zunyi 563099 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7028-4625","authenticated-orcid":false,"given":"Chaohong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathogen Biology School of Basic Medicine Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases Huazhong University of Science and Technology Wuhan Hubei China  Hubei 430074 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,16]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.7189\/jogh.12.04052"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.06.016"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-15-3532-1_2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo3923"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01592-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30818"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13016"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.114046"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10921"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2884-6"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-127615"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2017.05.003"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-019-00688-3"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2500\/ajr.2007.21.2970"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.08.018"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15054"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0812429"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.779"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2019.83267"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2020.09.033"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-020-00534-9"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.887"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2001750"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.663443"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0490-z"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aat4105"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03096"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00775-2"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20221483"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2884-6"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.593245"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00791-1"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-44391-9"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/2211-5463.12479"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3632"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.12.003"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14129"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-022-00973-6"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.06.003"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2017.10.023"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151620"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.ade7028"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S339254"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pccm.2024.02.002"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202403939","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202403939","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202403939","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T04:59:54Z","timestamp":1792299594000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202403939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,16]]},"references-count":44,"journal-issue":{"issue":"45","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1002\/advs.202403939"],"URL":"https:\/\/doi.org\/10.1002\/advs.202403939","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,16]]},"assertion":[{"value":"2024-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2403939"}}