DGK α and ζ Activities Control TH1 and TH17 Cell Differentiation

• Published in: Frontiers in immunology Vol. 10; p. 3048
• Main Authors: Yang, Jialong, Wang, Hong-Xia, Xie, Jinhai, Li, Lei, Wang, Jinli, Wan, Edwin C. K., Zhong, Xiao-Ping
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 15.01.2020
• Subjects: airway inflammation; DGK; Immunology; mTOR; Th differentiation; Th1; Th17
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.03048

CD4 + T helper (T H ) cells are critical for protective adaptive immunity against pathogens, and they also contribute to the pathogenesis of autoimmune diseases. How T H 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 H cell differentiation in a DGK dosage-dependent manner. A deficiency of either DGKα or ζ selectively impaired T H 1 differentiation without obviously affecting T H 2 and T H 17 differentiation. However, simultaneous ablation of both DGKα and ζ promoted T H 1 and T H 17 differentiation in vitro and in vivo , leading to exacerbated airway inflammation. Furthermore, we demonstrate that dysregulation of T H 17 differentiation of DGKα and ζ double-deficient CD4 + T cells was, at least in part, caused by increased mTOR complex 1/S6K1 signaling.