Lymph node fibroblastic reticular cells deposit fibrosis-associated collagen following organ transplantation
McGrath, Martina M
Lemos, Dario R
Shin, Su Ryon
Ware, Carl F
Bromberg, Jonathan S
JournalJournal of Clinical Investigation
PublisherAmerican Society of Clinical Oncology
MetadataShow full item record
AbstractAlthough 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 itemhttp://hdl.handle.net/10713/13548
- Senescence of fibroblastic reticular cells in draining lymph nodes: immunoregulation following transplantation.
- Authors: Sun Z, Burdick J
- Issue date: 2020 Aug 3
- Murine Fibroblastic Reticular Cells From Lymph Node Interact With CD4+ T Cells Through CD40-CD40L.
- Authors: Nakayama Y, Brinkman CC, Bromberg JS
- Issue date: 2015 Aug
- Repetitive ischemic injuries to the kidneys result in lymph node fibrosis and impaired healing.
- Authors: Maarouf OH, Uehara M, Kasinath V, Solhjou Z, Banouni N, Bahmani B, Jiang L, Yilmam OA, Guleria I, Lovitch SB, Grogan JL, Fiorina P, Sage PT, Bromberg JS, McGrath MM, Abdi R
- Issue date: 2018 Jul 12
- Lymph node fibroblastic reticular cell transplants show robust therapeutic efficacy in high-mortality murine sepsis.
- Authors: Fletcher AL, Elman JS, Astarita J, Murray R, Saeidi N, D'Rozario J, Knoblich K, Brown FD, Schildberg FA, Nieves JM, Heng TS, Boyd RL, Turley SJ, Parekkadan B
- Issue date: 2014 Aug 13
- The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture.
- Authors: Astarita JL, Cremasco V, Fu J, Darnell MC, Peck JR, Nieves-Bonilla JM, Song K, Kondo Y, Woodruff MC, Gogineni A, Onder L, Ludewig B, Weimer RM, Carroll MC, Mooney DJ, Xia L, Turley SJ
- Issue date: 2015 Jan