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    Lymph node fibroblastic reticular cells deposit fibrosis-associated collagen following organ transplantation

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    Author
    Li, Xiaofei
    Zhao, Jing
    Kasinath, Vivek
    Uehara, Mayuko
    Jiang, Liwei
    Banouni, Naima
    McGrath, Martina M
    Ichimura, Takaharu
    Fiorina, Paolo
    Lemos, Dario R
    Shin, Su Ryon
    Ware, Carl F
    Bromberg, Jonathan S
    Abdi, Reza
    Show allShow less

    Date
    2020-08-03
    Journal
    Journal of Clinical Investigation
    Publisher
    American Society of Clinical Oncology
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1172/JCI136618
    Abstract
    Although the immune response within draining lymph nodes (DLNs) has been studied for decades, how their stromal compartment contributes to this process remains to be fully explored. Here, we show that donor mast cells were prominent activators of collagen I deposition by fibroblastic reticular cells (FRCs) in DLNs shortly following transplantation. Serial analysis of the DLN indicated that the LN stroma did not return to its baseline microarchitecture following organ rejection and that the DLN contained significant fibrosis following repetitive organ transplants. Using several FRC conditional-knockout mice, we show that induction of senescence in the FRCs of the DLN resulted in massive production of collagen I and a proinflammatory milieu within the DLN. Stimulation of herpes virus entry mediator (HVEM) on FRCs by its ligand LIGHT contributed chiefly to the induction of senescence in FRCs and overproduction of collagen I. Systemic administration of ex vivo-expanded FRCs to mice decreased DLN fibrosis and strengthened the effect of anti-CD40L in prolonging heart allograft survival. These data demonstrate that the transformation of FRCs into proinflammatory myofibroblasts is critically important for the maintenance of a proinflammatory milieu within a fibrotic DLN.
    Keyword
    Fibrosis
    Immunology
    Organ transplantation
    Therapeutics
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/13548
    ae974a485f413a2113503eed53cd6c53
    10.1172/JCI136618
    Scopus Count
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    UMB Open Access Articles 2020

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