An enzyme called diacylglycerol kinase zeta (DGK?) appears to play an important role in suppressing runaway inflammation in asthma and may represent a novel therapeutic target, according to research presented at ATS 2019.
The researchers deleted the enzyme in mouse T cells, which drive the immune system, and found that both inflammation and airway hyperresponsiveness, two hallmarks of asthma, were reduced through independent biomolecular mechanisms.
We report that targeting DGK? protects against allergic asthma by simultaneously blocking airway inflammation and AHR by independent mechanisms. Targeted deletion of DGK? in T cells led to decreased type 2 inflammation with no attenuation of AHR through an ERK-dependent mechanism. In contrast, loss of DGK? in airway smooth muscle cells led to decreased AHR despite no changes in airway inflammation though an ERK-independent mechanism. Importantly, pharmacological inhibition of DGK diminished airway inflammation and AHR in mice, and also reduced bronchoconstriction of human airways.
These data suggest that DGK? is a novel therapeutic target for asthma and reveals that the inflammatory and AHR components of asthma are not as interdependent as generally believed.
