Research ArticleT CELLS

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

See allHide authors and affiliations

Science Immunology  04 Jan 2019:
Vol. 4, Issue 31, eaav1987
DOI: 10.1126/sciimmunol.aav1987

T cells need nuclear F-actin

T cell activation is regulated by numerous mechanisms upon T cell antigen receptor (TCR) engagement, including induction of specific cytokines by transcription factors like NF-κB and NFAT. Tsopoulidis et al. now show that TCR engagement causes rapid nuclear actin polymerization to create a dynamic actin filament network that is critical to CD4+ T cell effector functions. Nuclear actin filament polymerization involves the nuclear Arp2/3 complex that is induced by nuclear Ca2+ and regulated by N-Wasp and NIK. Specific inhibition of nuclear actin filament formation impairs T cell effector responses, including cytokine expression and CD4+ T cell help for antibody production. Together, these data reveal a role for nuclear actin filaments in driving CD4+ T cell effector functions.

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.

View Full Text