The role of protease-activated receptor 1 signaling in CD8 T cell effector functions

Hui Chen, Mindy Smith, Jasmin Herz, Tong Li, Rebecca Hasley, Cecile Le Saout, Ziang Zhu, Jie Cheng, Andres Gronda, José A. Martina, Pablo M. Irusta, Tatiana Karpova, Dorian B. McGavern, Marta Catalfamo

Research output: Contribution to journalArticlepeer-review

Abstract

CD8 T cells are essential for adaptive immunity against viral infections. Protease activated receptor 1 (PAR1) is expressed by CD8 T cells; however, its role in T cell effector function is not well defined. Here we show that in human CD8 T cells, PAR1 stimulation accelerates calcium mobilization. Furthermore, PAR1 is involved in cytotoxic T cell function by facilitating granule trafficking via actin polymerization and repositioning of the microtubule organizing center (MTOC) toward the immunological synapse. In vivo, PAR1−/− mice have reduced cytokine-producing T cells in response to a lymphocytic choriomeningitis virus (LCMV) infection and fail to efficiently control the virus. Specific deletion of PAR1 in LCMV GP33-specific CD8 T cells results in reduced expansion and diminished effector function. These data demonstrate that PAR1 plays a role in T cell activation and function, and this pathway could represent a new therapeutic strategy to modulate CD8 T cell effector function.

Original languageEnglish
Article number103387
JournaliScience
Volume24
Issue number11
DOIs
StatePublished - Nov 19 2021

Keywords

  • Immune response
  • Immunology
  • Molecular biology

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