Glycolysis and subsequent mevalonate biosynthesis play an important role in Th2 cell differentiation.

Yuichiro Yagi, Makoto Kuwahara, Junpei Suzuki, Yasushi Imai, Masakatsu Yamashita

Biochemical and biophysical research communications 2020 Sep 17

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Th2 cytokine such as IL-4, IL -5 and IL-13 are important therapeutic targets for Th2-type chronic inflammation. Several biologics targeting Th2 cytokine and its receptors are effective in clinical practice; however, the development of small-molecule compounds that inhibit Th2 cytokine productions is awaited. We found that an inhibitor for pyruvate dehydrogenase kinase (PDHK) suppresses the differentiation of IL-5/IL-13-producing Th2 cells. The expression of the Th2-related transcriptional factors Pparγ was decreased by treatment with inhibitor, whereas Gata3, a master regulator of Th2 cell differentiation, remained unchanged. The oxygen consumption rate was unaffected, whereas the level of farnesylated proteins was decreased by the PDHK inhibitor. Furthermore, the inhibitors for farnesyltransferase and hydroxymethylglutaryl-CoA reductase showed an inhibitory effect similar to that of the PDHK inhibitor. These results suggest that the mevalonate biosynthesis and subsequent protein prenylation may be novel therapeutic target for Th2 cell-dependent immune dysregulation, such as in allergic diseases. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Yuichiro Yagi, Makoto Kuwahara, Junpei Suzuki, Yasushi Imai, Masakatsu Yamashita. Glycolysis and subsequent mevalonate biosynthesis play an important role in Th2 cell differentiation. Biochemical and biophysical research communications. 2020 Sep 17;530(2):355-361