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

iScience (Nov 2021)

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

Affiliations

Hui Chen: Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC, USA; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Mindy Smith: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Jasmin Herz: Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
Tong Li: Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC, USA
Rebecca Hasley: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Cecile Le Saout: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Ziang Zhu: Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC, USA
Jie Cheng: Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC, USA
Andres Gronda: Department of Human Science, Georgetown University, Washington, DC, USA
José A. Martina: Cell and Developmental Biology Center, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
Pablo M. Irusta: Department of Human Science, Georgetown University, Washington, DC, USA
Tatiana Karpova: Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Dorian B. McGavern: Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
Marta Catalfamo: Department of Microbiology and Immunology, Georgetown University School of Medicine, Washington, DC, USA; Corresponding author

Journal volume & issue: Vol. 24, no. 11
p. 103387

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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