{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T00:14:00Z","timestamp":1793924040166,"version":"4.8.0"},"reference-count":39,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T00:00:00Z","timestamp":1620604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31600747"],"award-info":[{"award-number":["31600747"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,10]]},"abstract":"<jats:p>\n                    Trained immunity, induced by \u03b2-glucan in monocytes, is mediated by activating metabolic pathways that result in epigenetic rewiring of cellular functional programs; however, molecular mechanisms underlying these changes remain unclear. Here, we report a key immunometabolic and epigenetic pathway mediated by the\n                    <jats:italic>miR\u20139-5p<\/jats:italic>\n                    -isocitrate dehydrogenase 3\u03b1 (IDH3\u03b1) axis in trained immunity. We found that \u03b2-glucan\u2013trained\n                    <jats:italic>\n                      miR\u20139-5p\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    monocytes showed decreased IL-1\u03b2, IL-6, and TNF-\u03b1 production after LPS stimulation. Trained\n                    <jats:italic>\n                      miR\u20139-5p\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice produced decreased levels of proinflammatory cytokines upon rechallenge in vivo and had worse protection against\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    infection. miR\u20139-5p targeted IDH3\u03b1 and reduced \u03b1-ketoglutarate (\u03b1-KG) levels to stabilize HIF-1\u03b1, which promoted glycolysis. Accumulating succinate and fumarate via miR\u20139-5p action integrated immunometabolic circuits to induce histone modifications by inhibiting KDM5 demethylases. \u03b2-Glucan\u2013trained monocytes exhibited low IDH3\u03b1 levels, and IDH3\u03b1 overexpression blocked the induction of trained immunity by monocytes. Monocytes with IDH3\u03b1 variants from autosomal recessive retinitis pigmentosa patients showed a trained immunity phenotype at immunometabolic and epigenetic levels. These findings suggest that miR\u20139-5p and IDH3\u03b1 act as critical metabolic and epigenetic switches in trained immunity.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.144260","type":"journal-article","created":{"date-parts":[[2021,5,9]],"date-time":"2021-05-09T14:01:18Z","timestamp":1620568878000},"source":"Crossref","is-referenced-by-count":32,"title":["miR\u20139-5p regulates immunometabolic and epigenetic pathways in \u03b2-glucan\u2013trained immunity via IDH3\u03b1"],"prefix":"10.1172","volume":"6","author":[{"given":"Haibo","family":"Su","sequence":"first","affiliation":[{"name":"The Sixth Affiliated Hospital, GMU-GIBH Joint School of Life Science, Guangzhou Medical University, Guangzhou, China."},{"name":"State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongping","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Sixth Affiliated Hospital, Guangzhou Medical University, Qingyuan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ShuFeng","family":"Weng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaonan","family":"Sun","sequence":"additional","affiliation":[{"name":"The Sixth Affiliated Hospital, GMU-GIBH Joint School of Life Science, Guangzhou Medical University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Huang","sequence":"additional","affiliation":[{"name":"The Sixth Affiliated Hospital, GMU-GIBH Joint School of Life Science, Guangzhou 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