Research ArticleAllergy

Diacylglycerol kinase ζ promotes allergic airway inflammation and airway hyperresponsiveness through distinct mechanisms

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Science Signaling  03 Sep 2019:
Vol. 12, Issue 597, eaax3332
DOI: 10.1126/scisignal.aax3332

DGKζ activates airways

Asthma is characterized by both T cell–mediated inflammation and airway smooth muscle cell hyperreactivity. In T cells, activation stimulates production of the second messenger diglycerol (DAG), which is converted into phosphatidic acid by diacylglycerol kinase ζ (DGKζ) to terminate DAG signaling. In a mouse model of asthma, Singh et al. found that genetic and pharmacological inhibition of DGK activity reduced both airway contraction and allergic inflammation. Unexpectedly, loss of DGKζ in immune and nonimmune cells had separable effects on allergic inflammation in the lung and airway hyperreactivity. Thus, DGK activity in both T cells and smooth muscle cells contributes to asthma, which is responsive to DGK inhibition in mice.

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