{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:54:27Z","timestamp":1792616067448,"version":"4.5.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82060044"],"award-info":[{"award-number":["82060044"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid neoplasms characterized by treatment difficulties and a propensity to progress to acute myeloid leukemia. Impaired natural killer (NK) cell surveillance is a hallmark of MDS, yet the underlying molecular mechanisms remain poorly understood. This study aims to elucidate the mechanism by which HIF-1\u03b1 regulates NK cell differentiation disorders and its impact on NK cell cytotoxicity in MDS. Flow cytometry was employed to compare HIF-1\u03b1 expression and NK cell differentiation between wild-type and NUP98\/HOXD13 (NHD13) mice. Our results demonstrated a significant increase in HIF-1\u03b1 expression in the bone marrow and peripheral blood of MDS mice, accompanied by a notable decrease in immature NK cell subsets and activating receptors (NKG2D, NKp44, and DNAM-1). Overexpression of HIF-1\u03b1 in human NK cells or pharmacological stabilization with CoCl2 inhibits the differentiation into mature NK cells, suppresses the expression of degranulation molecules such as Granzyme B, and impairs NK cell cytotoxicity. Western blot analysis indicated that HIF-1\u03b1 regulates NK cell differentiation and function via the JAK1\/STAT5\/SOCS2 signaling pathway. Collectively, these findings suggest that the hypoxic microenvironment in MDS enhances HIF-1\u03b1 expression, which subsequently impairs NK cell maturation and inhibits their cytotoxicity. Targeting HIF-1\u03b1 may delay MDS progression by enhancing NK cell function via the JAK1\/STAT5\/SOCS2 signaling pathway.<\/jats:p>","DOI":"10.1093\/jimmun\/vkag059","type":"journal-article","created":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T19:05:08Z","timestamp":1776625508000},"source":"Crossref","is-referenced-by-count":2,"title":["HIF-1\u03b1 impairs NK cell differentiation-maturation and cytotoxicity in myelodysplastic syndrome via JAK1\/STAT5\/SOCS2 pathway"],"prefix":"10.1093","volume":"215","author":[{"given":"Shujuan","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Guilin Medical University , Guilin, Guangxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University , Harbin, Heilongjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengtao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Joint Surgery and Sports Medicine, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Xiangshan District , Guilin, Guangxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beili","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Guilin Medical University , Guilin, Guangxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Guilin Medical University , Guilin, Guangxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Guilin Medical University , Guilin, Guangxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianyi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Guilin Medical University , Guilin, Guangxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongfang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Guilin Medical University , Guilin, Guangxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Guilin Medical University , Guilin, Guangxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Guilin Medical University , Guilin, Guangxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1300-8586","authenticated-orcid":false,"given":"Xiaotao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Affiliated Hospital of Guilin Medical University , Guilin, Guangxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"2026041915050425800_vkag059-B1","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.1016\/S0140-6736(13)61901-7","article-title":"Myelodysplastic syndromes","volume":"383","author":"Ad\u00e8s","year":"2014","journal-title":"Lancet"},{"key":"2026041915050425800_vkag059-B2","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1001\/jama.2022.14578","article-title":"Diagnosis and treatment of myelodysplastic syndromes: a 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