DGK α and ζ Activities Control TH1 and TH17 Cell Differentiation.

Published online

Journal Article

CD4+ T helper (TH) cells are critical for protective adaptive immunity against pathogens, and they also contribute to the pathogenesis of autoimmune diseases. How TH 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 TH cell differentiation in a DGK dosage-dependent manner. A deficiency of either DGKα or ζ selectively impaired TH1 differentiation without obviously affecting TH2 and TH17 differentiation. However, simultaneous ablation of both DGKα and ζ promoted TH1 and TH17 differentiation in vitro and in vivo, leading to exacerbated airway inflammation. Furthermore, we demonstrate that dysregulation of TH17 differentiation of DGKα and ζ double-deficient CD4+ T cells was, at least in part, caused by increased mTOR complex 1/S6K1 signaling.

Full Text

Duke Authors

Cited Authors

  • Yang, J; Wang, H-X; Xie, J; Li, L; Wang, J; Wan, ECK; Zhong, X-P

Published Date

  • 2019

Published In

Volume / Issue

  • 10 /

Start / End Page

  • 3048 -

PubMed ID

  • 32010133

Pubmed Central ID

  • 32010133

Electronic International Standard Serial Number (EISSN)

  • 1664-3224

Digital Object Identifier (DOI)

  • 10.3389/fimmu.2019.03048

Language

  • eng

Conference Location

  • Switzerland