{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T11:59:32Z","timestamp":1777982372928,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["320030_205097"],"award-info":[{"award-number":["320030_205097"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory syndrome characterized by persistent activation of lymphocytes and macrophages. Recently, deleterious autosomal recessive mutations in\n                    <jats:italic>ZNFX1<\/jats:italic>\n                    were reported to predispose pediatric patients to HLH\u2010like disease upon viral trigger. The objective of this study was to assess the suitability of Znfx1\u2010mutant (Znfx1\n                    <jats:sup>mut<\/jats:sup>\n                    ) mice infected with lymphocytic choriomeningitis virus (LCMV) as a model of HLH\u2010like inflammation observed in patients. Following LCMV infection, Znfx1\n                    <jats:sup>mut<\/jats:sup>\n                    mice were monitored for pathophysiological signs of HLH, and their cells were immunophenotyped. Furthermore, functional assays were performed in vitro on T cells and bone marrow\u2010derived macrophages (BMDMs) to assess the cells\u2019 response to stimuli. Our experiments highlighted several hallmark features of HLH\u2010like inflammation in Znfx1\n                    <jats:sup>mut<\/jats:sup>\n                    mice. Immunophenotyping revealed more pronounced T cell expansion and type\u20101 helper (Th1) polarization in LCMV\u2010infected Znfx1\n                    <jats:sup>mut<\/jats:sup>\n                    mice. Znfx1\n                    <jats:sup>mut<\/jats:sup>\n                    macrophages infiltrated the liver to a greater extent upon infection and produced greater levels of cytokines in vitro in the absence of stimulation, suggesting that these cells have a major role in driving inflammation. This novel murine model of HLH\u2010like inflammation mirrors key aspects of the immune dysregulation observed in patients, providing a valuable tool for studying disease mechanisms in ZNFX1 deficiency.\n                  <\/jats:p>","DOI":"10.1002\/eji.70141","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T11:10:37Z","timestamp":1770203437000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Murine Model of Hemophagocytic Lymphohistiocytosis\u2010Like Inflammation in ZNFX1 Deficiency"],"prefix":"10.1002","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7292-8284","authenticated-orcid":false,"given":"Diana","family":"Tintor","sequence":"first","affiliation":[{"name":"Division of Immunology and University Children's Hospital Research Center University Children's Hospital Zurich  Zurich Switzerland"},{"name":"Pediatric Immunology Faculty of Medicine University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Milanesi","sequence":"additional","affiliation":[{"name":"Division of Immunology and University Children's Hospital Research Center University Children's Hospital Zurich  Zurich Switzerland"},{"name":"Pediatric Immunology Faculty of Medicine University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Division of Immunology and University Children's Hospital Research Center University Children's Hospital Zurich  Zurich Switzerland"},{"name":"Pediatric Immunology Faculty of Medicine University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"Lorenzini","sequence":"additional","affiliation":[{"name":"Division of Immunology and University Children's Hospital Research Center University Children's Hospital Zurich  Zurich Switzerland"},{"name":"Pediatric Immunology Faculty of Medicine University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3165-1441","authenticated-orcid":false,"given":"Severin","family":"Walser","sequence":"additional","affiliation":[{"name":"Division of Immunology and University Children's Hospital Research Center University Children's Hospital Zurich  Zurich Switzerland"},{"name":"Pediatric Immunology Faculty of Medicine University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyi","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Immunology and University Children's Hospital Research Center University Children's Hospital Zurich  Zurich Switzerland"},{"name":"Pediatric Immunology Faculty of Medicine University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julius","family":"K\u00f6ppen","sequence":"additional","affiliation":[{"name":"Division of Immunology and University Children's Hospital Research Center University Children's Hospital Zurich  Zurich Switzerland"},{"name":"Pediatric Immunology Faculty of Medicine University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achim","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Pathology University Hospital Zurich and University of Zurich  Zurich Switzerland"},{"name":"Institute of Molecular Cancer Research (IMCR) University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ola","family":"Sabet","sequence":"additional","affiliation":[{"name":"Division of Immunology and University Children's Hospital Research Center University Children's Hospital Zurich  Zurich Switzerland"},{"name":"Pediatric Immunology Faculty of Medicine University of Zurich  Zurich Switzerland"},{"name":"Children's Cancer Hospital Egypt 57357  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6653-9047","authenticated-orcid":false,"given":"Jana","family":"Pachlopnik Schmid","sequence":"additional","affiliation":[{"name":"Division of Immunology and University Children's Hospital Research Center University Children's Hospital Zurich  Zurich Switzerland"},{"name":"Pediatric Immunology Faculty of Medicine University of Zurich  Zurich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-020117-043625"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13298"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01102"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024025077"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00448"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2017.08.004"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1163316"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.03.045"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14081"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-023-01529-0"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010019\u20100416\u20100"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.08.006"},{"key":"e_1_2_13_15_1","doi-asserted-by":"crossref","unstructured":"K.Naydenova 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ZNFX1 an immunoregulatory RNA Helicase and E3 Ubiquitin Ligase Assembles into Pleiomorphic Polymers (2025). 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