T cell receptor-triggered nuclear actin network formation drives CD4 + T cell effector functions

Sci Immunol. 2019 Jan 4;4(31):eaav1987. doi: 10.1126/sciimmunol.aav1987.

Abstract

T cell antigen receptor (TCR) signaling triggers selective cytokine expression to drive T cell proliferation and differentiation required for immune defense and surveillance. The nuclear signaling events responsible for specificity in cytokine gene expression upon T cell activation are largely unknown. Here, we uncover formation of a dynamic actin filament network in the nucleus that regulates cytokine expression for effector functions of CD4+ T lymphocytes. TCR engagement triggers the rapid and transient formation of a nuclear actin filament network via nuclear Arp2/3 complex, induced by elevated nuclear Ca2+ levels and regulated via N-Wasp and NIK. Specific interference with TCR-induced formation of nuclear actin filaments impairs production of effector cytokines and prevents generation of antigen-specific antibodies but does not interfere with immune synapse formation and cell proliferation. Ca2+-regulated actin polymerization in the nucleus allows CD4+ T cells the rapid conversion of TCR signals into effector functions required for T cell help.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin-Related Protein 2-3 Complex / immunology
  • Actins / immunology*
  • Adoptive Transfer
  • Animals
  • Antigens / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Humans
  • Mice
  • Receptors, Antigen, T-Cell / immunology*

Substances

  • Actin-Related Protein 2-3 Complex
  • Actins
  • Antigens
  • Receptors, Antigen, T-Cell