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Here we report that plasma spermidine is correlated with the maturity of human newborns and reduced risk of inflammation. Administration of spermidine led to the remission of neonatal inflammation in mice. Mechanistic studies revealed that spermidine enhanced the generation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) via downstream eIF5A hypusination. Genetic deficiency or pharmacological inhibition of deoxyhypusine synthase (DHPS), a key enzyme of hypusinated eIF5A (eIF5A\n                    <jats:sup>Hyp<\/jats:sup>\n                    ), diminished the immunosuppressive activity of PMN-MDSCs, leading to aggravated neonatal inflammation. The eIF5A\n                    <jats:sup>Hyp<\/jats:sup>\n                    pathway was found to enhance the immunosuppressive function via histone acetylation\u2013mediated epigenetic transcription of immunosuppressive signatures in PMN-MDSCs. These findings demonstrate the spermidine-eIF5A\n                    <jats:sup>Hyp<\/jats:sup>\n                    metabolic axis as a master switch to restrict neonatal inflammation.\n                  <\/jats:p>","DOI":"10.1172\/jci183559","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T14:01:19Z","timestamp":1743429679000},"source":"Crossref","is-referenced-by-count":7,"title":["Spermidine restricts neonatal inflammation via metabolic shaping of polymorphonuclear myeloid-derived suppressor cells"],"prefix":"10.1172","volume":"135","author":[{"given":"Jiale","family":"Chen","sequence":"first","affiliation":[{"name":"Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China."},{"name":"Laboratory of Immunity, Inflammation and Cancer, Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, International Joint Laboratory of Ocular Diseases (Ministry of Education), State Key Laboratory of Experimental Hematology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohai","family":"Cui","sequence":"additional","affiliation":[{"name":"Tianjin Institute of 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