@article{f932f73050e1459dbb81fa805a84af18,
title = "The role of protease-activated receptor 1 signaling in CD8 T cell effector functions",
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.",
keywords = "Immune response, Immunology, Molecular biology",
author = "Hui Chen and Mindy Smith and Jasmin Herz and Tong Li and Rebecca Hasley and {Le Saout}, Cecile and Ziang Zhu and Jie Cheng and Andres Gronda and Martina, {Jos{\'e} A.} and Irusta, {Pablo M.} and Tatiana Karpova and McGavern, {Dorian B.} and Marta Catalfamo",
note = "Funding Information: Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number NIH R01AI145549-02 as well as the National Institute of Neurological Disorders and Stroke intramural program (DBM and JH). MC is supported in part by Leidos Biomedical Research, Inc . and has been funded in whole or in part with federal funds from the National Cancer Institute , NIH, under Contract HHSN261200800001E . The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. Funding Information: Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number NIH R01AI145549-02 as well as the National Institute of Neurological Disorders and Stroke intramural program (DBM and JH). MC is supported in part by Leidos Biomedical Research, Inc. and has been funded in whole or in part with federal funds from the National Cancer Institute, NIH, under Contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. MC conceived the study; PMI, DBM, and MC designed the experiments. HC, MS, TL, RH, AG, and JAM performed human CD8 T cell experiments. HC, JH, CL, TL, ZZ, and JC performed mouse experiments. TK guided microscopy acquisition and data analysis. HC, MS, and MC wrote the paper. JAM, PMI, and DBM critically reviewed the manuscript. The authors have no conflict of interest to declare. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = nov,
day = "19",
doi = "10.1016/j.isci.2021.103387",
language = "English",
volume = "24",
journal = "iScience",
issn = "2589-0042",
number = "11",
}