L-type voltage-gated Ca2+ channels control T cell killing via non-canonical Hedgehog signalling

ABSTRACT: Cytotoxic CD8+ T lymphocytes (CTLs) efficiently eliminate infected and cancerous cells throughout the body. T cell receptor (TCR)-induced Hedgehog signalling contributes to CTL-mediated killing, but how the pathway is activated downstream of the TCR is unknown. Here, we show that extracellular calcium (Ca2+) flux through L-type voltage-gated Ca2+ (Cav1) channels at the plasma membrane downstream of the TCR drives induction of the Hedgehog transcription factor Gli1, which is important for CTL killing in vitro and in vivo. This previously unknown non-canonical Hedgehog pathway is independent of canonical signalling and represents a primary mechanism of Gli1 induction in naïve CD8+ T cells, whereas CTLs can also activate Gli1 via MAPK. We further show that Cav1 channel-controlled Gli1 inducti

SUBMITTER: Flavio Beke 

PROVIDER: S-SCDT-10_1038-S44319-026-00810-8 | biostudies-other |

REPOSITORIES: biostudies-other