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Here, we investigated the effect of lithium on tryptophan breakdown via the kynurenine pathway using immortalized human microglia cells, primary human microglia isolated from surgical specimens, and microglia\u2010like cells differentiated from human induced pluripotent stem cells. Interferon (IFN)\u2010\u03b3, but not lipopolysaccharide, was able to activate immortalized human microglia, inducing a robust increase in indoleamine\u20102,3\u2010dioxygenase (\n                    <jats:italic>IDO1<\/jats:italic>\n                    ) mRNA transcription, IDO1 protein expression, and activity. Further, chromatin immunoprecipitation verified enriched binding of both STAT1 and STAT3 to the\n                    <jats:italic>IDO1<\/jats:italic>\n                    promoter. Lithium counteracted these effects, increasing inhibitory GSK3\u03b2\n                    <jats:sup>S9<\/jats:sup>\n                    phosphorylation and reducing STAT1\n                    <jats:sup>S727<\/jats:sup>\n                    and STAT3\n                    <jats:sup>Y705<\/jats:sup>\n                    phosphorylation levels in IFN\u2010\u03b3 treated cells. Studies in primary human microglia and hiPSC\u2010derived microglia confirmed the anti\u2010inflammatory effects of lithium, highlighting that IDO activity is reduced by GSK3 inhibitor SB\u2010216763 and STAT inhibitor nifuroxazide via downregulation of P\u2010STAT1\n                    <jats:sup>S727<\/jats:sup>\n                    and P\u2010STAT3\n                    <jats:sup>Y705<\/jats:sup>\n                    . Primary human microglia differed from immortalized human microglia and hiPSC derived microglia\u2010like cells in their strong sensitivity to LPS, resulting in robust upregulation of IDO1 and anti\u2010inflammatory cytokine IL\u201010. While lithium again decreased IDO1 activity in primary cells, it further increased release of IL\u201010 in response to LPS. Taken together, our study demonstrates that lithium inhibits the inflammatory kynurenine pathway in the microglia compartment of the human brain.\n                  <\/jats:p>","DOI":"10.1002\/glia.24123","type":"journal-article","created":{"date-parts":[[2021,12,4]],"date-time":"2021-12-04T11:14:26Z","timestamp":1638616466000},"page":"558-571","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Lithium inhibits tryptophan catabolism via the inflammation\u2010induced kynurenine pathway in human microglia"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4756-7381","authenticated-orcid":false,"given":"Ria","family":"G\u00f6ttert","sequence":"first","affiliation":[{"name":"Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin Humboldt\u2010Universit\u00e4t zu Berlin, and Berlin Institute of Health, Klinik f\u00fcr Neurologie und Abteilung 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