DGK α and ζ Activities Control T1 and T17 Cell Differentiation.

CD4 T helper (T) cells are critical for protective adaptive immunity against pathogens, and they also contribute to the pathogenesis of autoimmune diseases. How T differentiation is regulated by the TCR's downstream signaling is still poorly understood. We describe here that diacylglycerol kinases (DGKs), which are enzymes that convert diacylglycerol (DAG) to phosphatidic acid, exert differential effects on T cell differentiation in a DGK dosage-dependent manner. A deficiency of either DGKα or ζ selectively impaired T1 differentiation without obviously affecting T2 and T17 differentiation. However, simultaneous ablation of both DGKα and ζ promoted T1 and T17 differentiation and , leading to exacerbated airway inflammation. Furthermore, we demonstrate that dysregulation of T17 differentiation of DGKα and ζ double-deficient CD4 T cells was, at least in part, caused by increased mTOR complex 1/S6K1 signaling.