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HES in human patients is defined by 1.5 \u00d7 109 cells\/L circulating in the blood with end-organ infiltration and resultant tissue damage. In mice lacking the NIK gene (Map3k14), the mechanisms underlying eosinophilopoiesis have not been fully elucidated, although previous studies have demonstrated a connection between Th2 helper T cells and HES in Nik\u2212\/\u2212 mice. We hypothesize that NIK also influences the development and education of eosinophils in the hematopoietic tissues independent of T-cell involvement. We developed an in vitro bone marrow microenvironment, and utilized MTT and BrdU assays coupled with cytology, flow cytometry, BCL-XL ELISA, and an inflammation antibody array to show that Nik\u2212\/\u2212 eosinophils demonstrate altered metabolism, survival, and maturation when compared to wild-type eosinophils in response to an altered microenvironment and cytokine milieu. Furthermore, the Nik\u2212\/\u2212 in vitro bone marrow microenvironment contains lower levels of free tumor necrosis factor receptor 1 (TNFR1) and more consistent surface-bound TNFR1 when compared to wild-type counterparts. Additionally, we explored the heterogeneity of granulocyte differentiation in the Nik\u2212\/\u2212 model. Here, we demonstrate that in vivo, Nik\u2212\/\u2212 mice contain significantly higher counts of both mature and immature eosinophils, and a population of eosinophils expressing neutrophil marker Ly6G, which may represent a unique population subset of eosinophils. Overall, these data indicate that NIK influences eosinophil maturation, differentiation, and responsiveness to the surrounding microenvironment.<\/jats:p>","DOI":"10.1093\/jleuko\/qiag028","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T12:42:24Z","timestamp":1772109744000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of NF-\u03baB-inducing kinase (NIK) affects eosinophilopoiesis in a murine model of Hypereosinophilic syndrome"],"prefix":"10.1093","volume":"118","author":[{"given":"Brie","family":"Trusiano","sequence":"first","affiliation":[{"name":"Department of Biomedical Science and Pathobiology, Virginia Tech, Virginia Maryland College of Veterinary Medicine , 205 Duck Pond Drive, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebekah A","family":"Smith","sequence":"additional","affiliation":[{"name":"College of Science, Department of Biological Sciences, Virginia Tech , 926 West Campus Drive, Blacksburg, VA 24073, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5992-9028","authenticated-orcid":false,"given":"Cassandra S","family":"Poole","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Pathobiology, Virginia Tech, Virginia Maryland College of Veterinary Medicine , 205 Duck Pond Drive, Blacksburg, VA 24061, USA"},{"name":"Graduate Program in Biomedical and Veterinary Sciences, Virginia Polytechnic Institute and State University , 205 Duck Pond Drive, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly A","family":"Morrison","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Pathobiology, Virginia Tech, Virginia Maryland College of Veterinary Medicine , 205 Duck Pond Drive, Blacksburg, VA 24061, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxx","family":"Steinmann","sequence":"additional","affiliation":[{"name":"College of Science, Department of Biological Sciences, Virginia Tech , 926 West Campus Drive, Blacksburg, VA 24073, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9573-5250","authenticated-orcid":false,"given":"Irving C","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science and Pathobiology, Virginia Tech, Virginia Maryland College of Veterinary Medicine , 205 Duck Pond Drive, Blacksburg, VA 24061, USA"},{"name":"Graduate Program in Biomedical and Veterinary Sciences, Virginia Polytechnic Institute and State University , 205 Duck Pond Drive, Blacksburg, VA 24061, USA"},{"name":"Graduate Program in Translational Biology, Medicine and Health, Virginia Polytechnic Institute and State University , 1 Riverside Circle, Roanoke, VA 24016, 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