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The expression of EBI3 gene is induced by Toll\u2010like receptors (TLRs). Repeated treatment with imiquimod (IMQ), a TLR7 agonist, induces splenomegaly and cytopaenia due to increased splenic function. Although immune cell activation is speculated to play a role in chronic infection\u2010mediated splenomegaly, the detailed mechanisms remain unknown. This study shows that IMQ treatment induces marked splenomegaly and severe bicytopaenia (anaemia and thrombocytopaenia) in wild\u2010type mice. In IMQ\u2010treated mice, myeloid cell populations in the spleen increased, and extramedullary haematopoiesis was observed. RNA\u2010seq analysis revealed the upregulation of type I interferon (IFN)\u2010related genes in the spleens of IMQ\u2010treated mice. IMQ\u2010induced pathological changes were partially mitigated by EBI3 deficiency. To investigate the mechanism of the improved phenotypes in the <jats:italic>Ebi3<\/jats:italic> KO mice, we examined the involvement of IL\u201027, a heterodimer of EBI3 and IL\u201027p28. The expression of <jats:italic>Il27a<\/jats:italic>, which encodes IL\u201027p28, was increased in the spleen and peripheral blood by IMQ treatment. Furthermore, IL\u201027 stimulation upregulated type I IFN\u2010related genes in bone marrow\u2010derived macrophage cultures without type I IFN. These findings suggest that EBI3 deficiency mitigated IMQ\u2010mediated pathological changes, presumably via a lack of IL\u201027 formation. Our study thus provides insights into the molecular mechanisms underlying chronic infection\u2010mediated splenomegaly.<\/jats:p>","DOI":"10.1111\/imm.13905","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T06:06:26Z","timestamp":1738130786000},"page":"36-51","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Epstein\u2013Barr Virus\u2010Induced 3 Attributes to <scp>TLR7<\/scp>\u2010Mediated Splenomegaly"],"prefix":"10.1111","volume":"175","author":[{"given":"Masanori","family":"Iseki","sequence":"first","affiliation":[{"name":"Department of Immunology and Molecular Genetics Kawasaki Medical School  Kurashiki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuma","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Genetics Kawasaki Medical School  Kurashiki 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