{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T14:46:17Z","timestamp":1782398777999,"version":"3.54.5"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":175,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202021"],"award-info":[{"award-number":["82202021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270606"],"award-info":[{"award-number":["82270606"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370578"],"award-info":[{"award-number":["82370578"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Immune dysregulation is a key driver of metabolic dysfunction\u2010associated steatotic liver disease (MASLD). Double\u2010negative regulatory T (DNT) cells, which are essential for hepatic immune homeostasis, are functionally impaired in MASLD. CD39, an ectoenzyme that converts ATP to adenosine, sustains DNT cell viability and immunoregulatory function. However, the mechanisms of MASLD\u2010induced CD39 dysregulation remain unknown. In this study, a transcriptomic analysis of hepatic DNT cells from MASLD mice revealed reduced ATP hydrolysis, as confirmed by flow cytometry, and lower CD39 level compared to normal control diet\u2010fed mice. Similarly, single\u2010cell transcriptomic data showed that CD39 was downregulated in hepatic DNT cells from MASLD patients, and higher CD39 expression was associated with enhanced cytotoxicity and viability. Furthermore,\n                    <jats:italic>in vitro<\/jats:italic>\n                    experiments confirmed that CD39 maintained the immunosuppressive function of DNT cells by hydrolyzing ATP and suppressing monocyte activation. Mechanistically, arachidonic acid (AA), which is enriched in the livers of MASLD, suppressed CD39 via hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1). This AA\u2010HIF\u20101\u03b1\u2010CD39 axis impaired DNT cell\u2010mediated monocyte immunosuppression, accelerating immune imbalance and MASLD progression. These findings establish the AA\u2010HIF\u20101\u03b1\u2010CD39 axis as a key pathway driving DNT cell dysfunction in MASLD, highlighting potential therapeutic strategies targeting metabolic\u2013immune crosstalk to restore hepatic immune balance.\n                  <\/jats:p>","DOI":"10.1155\/jimr\/6950401","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T13:48:48Z","timestamp":1782395328000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatic Arachidonic Acid Dysregulation Impairs Double\u2010Negative Regulatory T Cell\u2010Mediated Immunoregulation via CD39 Downregulation and Drives MASLD Development"],"prefix":"10.1155","volume":"2026","author":[{"given":"Hua","family":"Jin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3404-5173","authenticated-orcid":false,"given":"Dong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1379-5752","authenticated-orcid":false,"given":"Guangyong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-025-00599-1"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/egastro-2023-100019"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.10.009"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-10-050625"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2022.02.019"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-20941-x"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062512"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2024.11.039"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106632"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.066"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.06.044"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2024.156127"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.038"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00727"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI138519"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114636"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.363"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201095200"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.3945\/an.114.007732"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26020788"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.009"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2018.07.022"}],"container-title":["Journal 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