Suppression of caspase 8 activity by a coronin 1-PI3Kδ pathway promotes T cell survival independently of TCR and IL-7 signaling

Sci Signal. 2021 Dec 21;14(714):eabj0057. doi: 10.1126/scisignal.abj0057. Epub 2021 Dec 21.

Abstract

The control of T cell survival is crucial for defense against infectious pathogens or emerging cancers. Although the survival of peripheral naïve T cells has been proposed to be controlled by interleukin-7 (IL-7) signaling and T cell receptor (TCR) activation by peptide-loaded major histocompatibility complexes (pMHC), the essential roles for these pathways in thymic output and T cell proliferation have complicated the analysis of their contributions to T cell survival. Here, we showed that the WD repeat–containing protein coronin 1, which is dispensable for thymic selection and output, promoted naïve T cell survival in the periphery in a manner that was independent of TCR and IL-7 signaling. Coronin 1 was required for the maintenance of the basal activity of phosphoinositide 3-kinase δ (PI3Kδ), thereby suppressing caspase 8–mediated apoptosis. These results therefore reveal a coronin 1–dependent PI3Kδ pathway that is independent of pMHC:TCR and IL-7 signaling and essential for peripheral T cell survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone* / analogs & derivatives
  • Animals
  • Caspase 8* / genetics
  • Caspase 8* / metabolism
  • Cell Survival
  • Interleukin-7*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Antigen, T-Cell*
  • T-Lymphocytes* / metabolism

Substances

  • Interleukin-7
  • Receptors, Antigen, T-Cell
  • coronin
  • Casp8 protein, mouse
  • Caspase 8
  • 4-Butyrolactone