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Regular article Vascular biology, atherosclerosis, and endothelium biology| Volume 191, ISSUE 2, P396-414, February 01, 2021

High Endothelial Venules Accelerate Naive T Cell Recruitment by Tumor Necrosis Factor-Mediated R-Ras Upregulation

  • Junko Sawada
    Affiliations
    Cancer and Blood Disorders Institute and Institute for Fundamental Biomedical Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida

    Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, St. Petersburg, Florida
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  • Carole Y. Perrot
    Affiliations
    Cancer and Blood Disorders Institute and Institute for Fundamental Biomedical Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida

    Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, St. Petersburg, Florida
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  • Linyuan Chen
    Affiliations
    Cancer and Blood Disorders Institute and Institute for Fundamental Biomedical Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida

    Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, St. Petersburg, Florida
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  • Ashley E. Fournier-Goss
    Affiliations
    Cancer and Blood Disorders Institute and Institute for Fundamental Biomedical Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida

    Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, St. Petersburg, Florida
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  • Jeremiah Oyer
    Affiliations
    Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, St. Petersburg, Florida

    Burnett School of Biomedical Sciences, University of Central Florida, Orlando Florida
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  • Alicja Copik
    Affiliations
    Burnett School of Biomedical Sciences, University of Central Florida, Orlando Florida
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  • Masanobu Komatsu
    Correspondence
    Address correspondence to Masanobu Komatsu, Ph.D., Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, 600 5th St. S., St. Petersburg, FL 33701.
    Affiliations
    Cancer and Blood Disorders Institute and Institute for Fundamental Biomedical Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida

    Tumor Microenvironment and Cancer Immunology Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla California
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Published:November 04, 2020DOI:https://doi.org/10.1016/j.ajpath.2020.10.009
      Recruitment of naive T cells to lymph nodes is essential for the development of adaptive immunity. Upon pathogen infection, lymph nodes promptly increase the influx of naive T cells from the circulation in order to screen and prime the T cells. The precise contribution of the lymph node vasculature to the regulation of this process remains unclear. Here we show a role for the Ras GTPase, R-Ras, in the functional adaptation of high endothelial venules to increase naive T cell trafficking to the lymph nodes. R-Ras is transiently up-regulated in the endothelium of high endothelial venules by the inflammatory cytokine tumor necrosis factor (TNF) within 24 hours of pathogen inoculation. TNF induces R-Ras upregulation in endothelial cells via JNK and p38 mitogen-activated protein kinase but not NF-κB. Studies of T cell trafficking found that the loss of function of endothelial R-Ras impairs the rapid acceleration of naive T cell recruitment to the lymph nodes upon inflammation. This defect diminished the ability of naive OT-1 T cells to develop antitumor activity against ovalbumin-expressing melanoma. Proteomic analyses suggest that endothelial R-Ras facilitates TNF-dependent transendothelial migration (diapedesis) of naive T cells by modulating molecular assembly the at T cell–endothelial cell interface. These findings give new mechanistic insights into the functional adaptation of high endothelial venules to accelerate naive T cell recruitment to the lymph nodes.
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      • Correction
        The American Journal of PathologyVol. 191Issue 6
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          In the article entitled, “High Endothelial Venules Accelerate Naive T Cell Recruitment by Tumor Necrosis Factor-Mediated R-Ras Upregulation” (Volume 191, pages 396-414 of the February 2021 issue of The American Journal of Pathology; DOI: https://doi.org/10.1016/j.ajpath.2020.10.009) the authors have discovered an error in the primer sequences presented in the first paragraph of the Materials and Methods section: Mice and Tumor Model. The second sequence for Cre-recombination detection is incorrect and should be replaced.
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