Lymph node fibroblastic reticular cells deposit fibrosis-associated collagen following organ transplantation
Author
Li, XiaofeiZhao, 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
Date
2020-08-03Journal
Journal of Clinical InvestigationPublisher
American Society of Clinical OncologyType
Article
Metadata
Show full item recordAbstract
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.Identifier to cite or link to this item
http://hdl.handle.net/10713/13548ae974a485f413a2113503eed53cd6c53
10.1172/JCI136618