Chronic allograft rejection: a fresh look.
Curr Opin Organ Transplant
; 20(1): 13-20, 2015 Feb.
Article
en En
| MEDLINE
| ID: mdl-25563987
ABSTRACT
PURPOSE OF REVIEW New developments suggest that the graft itself and molecules expressed within the graft microenvironment dictate the phenotype and evolution of chronic rejection. RECENT FINDINGS:
Once ischemia-reperfusion injury, cellular and humoral immune responses target the microvasculature, the associated local tissue hypoxia results in hypoxia-inducible factor 1α-dependent expression of pro-inflammatory and proangiogenic growth factors including vascular endothelial growth factor (VEGF) as a physiological response to injury. Local expression of VEGF can promote the recruitment of alloimune T cells into the graft. mTOR/Akt signaling within endothelial cells regulates cytokine- and alloantibody-induced activation and proliferation and their proinflammatory phenotype. Inhibition of mTOR and/or Akt results in an anti-inflammatory phenotype and enables the expression of coinhibitory molecules that limit local T cell reactivation and promotes immunoregulation. Semaphorin family molecules may bind to neuropilin-1 on regulatory T cell subsets to stabilize functional responses. Ligation of neuropilin-1 on Tregs also inhibits Akt-induced responses suggesting common theme for enhancing local immunoregulation and long-term graft survival.SUMMARY:
Events within the graft initiated by mTOR/Akt-induced signaling promote the development of chronic rejection. Semaphorin-neuropilin biology represents a novel avenue for targeting this biology and warrants further investigation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Trasplante de Órganos
/
Rechazo de Injerto
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Opin Organ Transplant
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA