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We previously demonstrated that murine iPSC\u2010microglia and iPSC\u2010macrophages display phenotypical activation properties highly comparable to microglia and macrophages in vivo<jats:italic>.<\/jats:italic> Here we extended the characterization of iPSC\u2010microglia and iPSC\u2010macrophages with the analysis of their transcriptome profile. Next, these cellular models were employed to evaluate neuroimmune toxicity in vitro and to investigate the immune\u2010modulatory properties of interleukin 13 (IL13), a cytokine known for its ability to protect against neuroinflammation\u2010induced pathology by modulating microglia and macrophage activation. iPSC\u2010microglia and iPSC\u2010macrophages, in co\u2010culture with astrocyte\u2010committed neural stem cells (NSC), were (pre)treated with IL13 and stimulated with lipopolysaccharide (LPS) and interferon \u03b3 (IFN\u03b3), to assess how IL13 modulates their inflammatory response. Additionally, the use of luciferase\u2010expressing NSC (Luc\u2010NSC) allowed real\u2010time monitoring of immune\u2010mediated neurotoxicity. Despite the known anti\u2010inflammatory properties of IL13, iPSC\u2010microglia primed with IL13 before LPS\u2009+\u2009IFN\u03b3 stimulation significantly increased NO secretion. This was associated with a marked reduction of the luminescence signal produced by Luc\u2010NSC. Interestingly, we observed that IL13 signaling has a divergent functional outcome in microglia as compared to macrophages, as for the latter no major alterations in NO release and Luc\u2010NSC viability were observed upon IL13 (pre)treatment. Finally, the striking IL13\u2010induced upregulation of NO secretion by microglia under pro\u2010inflammatory conditions was confirmed in vivo, where intracerebral delivery of IL13 increased inducible nitric oxide synthase mRNA expression. Concluding, we applied iPSC\u2010derived neuroimmune cell culture models to identify distinct neuroimmune (toxicity) responses of microglia and macrophages to IL13\u2010based immune modulation.<\/jats:p>","DOI":"10.1002\/glia.23899","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T12:25:38Z","timestamp":1598876738000},"page":"326-345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Murine induced pluripotent stem cell\u2010derived neuroimmune cell culture models emphasize opposite immune\u2010effector functions of interleukin 13\u2010primed microglia and macrophages in terms of neuroimmune toxicity"],"prefix":"10.1002","volume":"69","author":[{"given":"Alessandra","family":"Quarta","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Hematology University of Antwerp  Antwerp Belgium"},{"name":"Vaccine and Infectious Disease Institute (Vaxinfectio), University 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