{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:17:46Z","timestamp":1790025466225,"version":"4.0.1"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Basic Science Research Program through the National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-00518438"],"award-info":[{"award-number":["RS-2025-00518438"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Sepsis is a life-threatening syndrome characterized by dysregulated host responses to infection. In addition to early hyperinflammation, many patients develop profound immune suppression, and multiple targeted immunotherapies have failed to improve outcomes, highlighting the need for actionable biomarkers and new therapeutic strategies. Here, we integrated metabolomic and transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) and splenocytes in rat models of polymicrobial sepsis to identify metabolites associated with immune dysfunction. Candidate findings were validated using in vivo supplementation studies and in vitro functional assays, and clinical relevance was assessed in PBMCs from patients with sepsis and healthy volunteers. Across omics datasets, intracellular aspartate (ASP) was consistently reduced in immune cells during sepsis and was associated with features of immune paralysis. Supplementation with L-ornithine L-aspartate (LOLA), an ASP source, improved survival in septic rats, enhanced bacterial clearance, and mitigated acute kidney injury. In vitro, pharmacologic or genetic disruption of ASP production impaired phagocytosis and cytokine responses, which were partially rescued by ASP supplementation. Consistently, patients with sepsis exhibited lower intracellular ASP levels in PBMCs than healthy volunteers. Together, these results support a critical role for ASP in maintaining immune competence during sepsis and suggest that intracellular ASP may serve as a biomarker of immune suppression and a potential therapeutic target.<\/jats:p>","DOI":"10.3390\/cells15060513","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T15:06:22Z","timestamp":1773414382000},"page":"513","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of Aspartate in Immune Response and Mortality in a Polymicrobial Sepsis Model: Insights from Metabolomics and Transcriptomics"],"prefix":"10.3390","volume":"15","author":[{"given":"Min Ji","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8148-0127","authenticated-orcid":false,"given":"Bo Mi","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se Rin","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6047-6416","authenticated-orcid":false,"given":"Seongmin","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye Jin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kihwan","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8826-1787","authenticated-orcid":false,"given":"Chang June","family":"Yune","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3537-4136","authenticated-orcid":false,"given":"Tae Nyoung","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9605-7965","authenticated-orcid":false,"given":"Jinkun","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9331-7805","authenticated-orcid":false,"given":"Nam Joo","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7233-1261","authenticated-orcid":false,"given":"Jiwon","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han A Reum","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiewan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1469-839X","authenticated-orcid":false,"given":"Dong-Hyuk","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Heon","family":"Noh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Chungnam National University, Daejeon 34134, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chungoo","family":"Park","sequence":"additional","affiliation":[{"name":"School of Biological Science and Technology, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2271-3434","authenticated-orcid":false,"given":"Sangchun","family":"Choi","sequence":"additional","affiliation":[{"name":"Emergency Department, Soonchunhyang University College of Medicine, Asan 31538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choong Hwan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7991-9428","authenticated-orcid":false,"given":"Kyuseok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, CHA University School of Medicine, Seongnam 13496, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1001\/jama.2020.2717","article-title":"Prevalence and Outcomes of Infection Among Patients in Intensive Care Units in 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