Autocrine IFN-I inhibits isocitrate dehydrogenase in the TCA cycle of LPS-stimulated macrophages
- De Souza, DP; Achuthan, A; Lee, MK; Binger, KJ; Lee, MC; Davidson, S; Tull, DL; McConville, MJ; Cook, AD; Murphy, AJ; Hamilton, JA; Fleetwood, AJ;
Publication Year 2019-10-01, Volume 129, Issue #10, Page 4239-4244
- Journal Title
- Journal of Clinical Investigation
- Publication Type
- Journal Article
- Macrophage activation in response to LPS is coupled to profound metabolic changes, typified by accumulation of the TCA cycle intermediates citrate, itaconate, and succinate. We have identified that endogenous type I IFN controls the cellular citrate/alpha-ketoglutarate ratio and inhibits expression and activity of isocitrate dehydrogenase (IDH); and, via 13C-labeling studies, demonstrated that autocrine type I IFN controls carbon flow through IDH in LPS-activated macrophages. We also found that type I IFN-driven IL-10 contributes to inhibition of IDH activity and itaconate synthesis in LPS-stimulated macrophages. Our findings have identified the autocrine type I IFN pathway as being responsible for the inhibition of IDH in LPS-stimulated macrophages.
- WEHI Research Division(s)
- PubMed ID
- Link To PubMed Central Version
- Publisher's Version
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- Refer to copyright notice on published article.
Creation Date: 2019-09-20 10:16:30Last Modified: 2020-02-03 08:15:02