AUTHOR=Yang Jialong , Wang Hong-Xia , Xie Jinhai , Li Lei , Wang Jinli , Wan Edwin C. K. , Zhong Xiao-Ping 

TITLE=DGK α and ζ Activities Control TH1 and TH17 Cell Differentiation

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.03048

DOI=10.3389/fimmu.2019.03048

ISSN=1664-3224

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