{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:45:06Z","timestamp":1790610306100,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009561","name":"American Partnership for Eosinophilic Disorders","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009561","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006792","name":"Hartwell Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019212","name":"American Academy of Allergy, Asthma and Immunology Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019212","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5T32AI055428\u201019"],"award-info":[{"award-number":["5T32AI055428\u201019"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Eosinophilic Esophagitis (EoE) is a chronic food allergy that causes esophageal inflammation and fibrosis and manifests with symptoms of reflux, chest pain, swallowing difficulty, and food impactions. Though the prevalence of EoE is increasing by ~15% each year, our understanding of EoE immunopathology is limited. A noted feature of EoE is the presence of food\u2010specific IgG4 antibodies in the circulation and esophageal tissue. Production of IgG4 is confined to IL\u201010<jats:sup>+<\/jats:sup> B cells (Bregs) in other allergic diseases, suggesting Bregs may be present in EoE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We examined circulating Bregs in patients with EoE milk allergy. In parallel, we performed mechanistic investigations of the role of Bregs in a murine model of food\u2010antigen\u2010dependent EoE. Flow cytometry and histologic analyses were used to assess esophageal and draining lymph node immune cells, and in\u00a0vitro assays were used to evaluate Breg functional capacity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Breg frequency was reduced in both EoE milk allergic subjects and an EoE disease model. Murine Breg suppressive capacity was impaired during EoE\u2010like inflammation. Inducible deletion of Breg\u2010derived IL\u201010 worsened EoE\u2010like inflammation, while adoptive transfer of IL\u201010 sufficient Bregs suppressed DC activation and improved esophageal eosinophilia. IFN\u03b3 was sufficient to suppress Breg expansion and IL\u201010 production in\u00a0vitro and contributed to Breg dysfunction and esophageal inflammation in\u00a0vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Bregs play an immunoregulatory role during EoE by controlling esophageal eosinophilia but are functionally impaired due to IFN\u03b3\u2010mediated signaling. These findings have important implications for understanding EoE's etiology and implementing future therapies that target IFN\u03b3.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.16594","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T08:12:25Z","timestamp":1747642345000},"page":"2824-2836","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>IFN\u03b3<\/scp> Signaling Impairs Regulatory B Cell Function Resulting in Worse Control of Esophageal Food Allergy"],"prefix":"10.1111","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1422-9140","authenticated-orcid":false,"given":"Rachel L.","family":"Clement","sequence":"first","affiliation":[{"name":"Institute for Immunology and Immune Health Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Division of Allergy and Immunology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4655-0799","authenticated-orcid":false,"given":"Julie","family":"Dilollo","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric M.","family":"Rodr\u00edguez\u2010L\u00f3pez","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Immune Health Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Division of Allergy and Immunology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cleandre M.","family":"Guerrier","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9286-4268","authenticated-orcid":false,"given":"David A.","family":"Hill","sequence":"additional","affiliation":[{"name":"Institute for Immunology and Immune Health Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Division of Allergy and Immunology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2020.1806054"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.06.067"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15231"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e318291fee2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1502863"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2020.03.020"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2015.09.005"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-012-0608-x"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3181788282"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002323"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpepsy\/jsx117"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2017.07.025"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.14920"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.09.042"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.11.011"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2022.01.019"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2022.12.014"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.16279"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.06.065"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15694"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI125917"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2000973"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/cti.2016.30"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2010.10.027"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2008.03.005"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2025.101466"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.611795"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14763"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6605"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.23633"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/cea.12238"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.03.017"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.4168\/aair.2018.10.3.236"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2012.01.005"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2010.05.013"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2010.0020"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.01.014"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.13486"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.02.049"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/ACI.0b013e328338cbab"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002227"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.02.024"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15826"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500971"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11501"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2017.04.010"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14854"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2025.01.008"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3281"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.12.635"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15779"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-1736-6_15"},{"key":"e_1_2_9_54_1","first-page":"25","article-title":"Increased Regulatory T Cells in Peripheral Blood of Children With Eosinophilic Esophagitis","volume":"14","author":"Abdolahi M.","year":"2021","journal-title":"Gastroenterology and Hepatology From Bed to Bench"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aller.2019.02.005"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12937"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep19685"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.07.041"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-68660-9"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.243543"}],"container-title":["Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/all.16594","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T10:45:40Z","timestamp":1759315540000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/all.16594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,19]]},"references-count":59,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1111\/all.16594"],"URL":"https:\/\/doi.org\/10.1111\/all.16594","archive":["Portico"],"relation":{},"ISSN":["0105-4538","1398-9995"],"issn-type":[{"value":"0105-4538","type":"print"},{"value":"1398-9995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,19]]},"assertion":[{"value":"2024-10-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}