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Curr Opin Organ Transplant. 2016 Jun;21(3):253-7. doi: 10.1097/MOT.0000000000000314.

Innate immune mechanisms in transplant allograft vasculopathy.

Author information

1
aDepartment of Cardiovascular Medicine bDepartment of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.

Abstract

PURPOSE OF REVIEW:

Allograft vasculopathy is the leading cause of late allograft loss following solid organ transplantation. Ischemia reperfusion injury and donor-specific antibody-induced complement activation confer heightened risk for allograft vasculopathy via numerous innate immune mechanisms, including MyD88, high-mobility group box 1 (HMGB1), and complement-induced noncanonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling.

RECENT FINDINGS:

The role of MyD88, a signal adaptor downstream of the Toll-like receptors (TLR), has been defined in an experimental heart transplant model, which demonstrated that recipient MyD88 enhanced allograft vasculopathy. Importantly, triggering receptor on myeloid receptor 1, a MyD88 amplifying signal, was present in rejecting human cardiac transplant biopsies and enhanced the development of allograft vasculopathy in mice. HMGB1, a nuclear protein that activates Toll-like receptors, also enhanced the development of allograft vasculopathy. Complement activation elicits assembly of membrane attack complexes on endothelial cells which activate noncanonical NF-κB signaling, a novel complement effector pathway that induces proinflammatory genes and potentiates endothelial cell-mediated alloimmune T-cell activation, processes which enhance allograft vasculopathy.

SUMMARY:

Innate immune mediators, including HMGB1, MyD88, and noncanonical NF-κB signaling via complement activation contribute to allograft vasculopathy. These pathways represent potential therapeutic targets to reduce allograft vasculopathy after solid organ transplantation.

PMID:
27077602
PMCID:
PMC4903161
DOI:
10.1097/MOT.0000000000000314
[Indexed for MEDLINE]
Free PMC Article

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