Dusan Hanidziar1, Maria Koulmanda. 1. Transplant Institute, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA 02215, USA.
Abstract
PURPOSE OF REVIEW: Inflammation of the allograft, occurring as a consequence of hypoxia and ischemia/reperfusion injury, adversely influences short-term and long-term transplant outcomes. Thus far, imbalance of tissue-protective Treg and tissue-destructive Th17 cells has been confirmed in a number of tissue-inflammatory states, including autoimmune disease. Hence, benefits of tilting Treg-Th17 equilibrium toward dominance of Tregs may promote transplant tolerance. RECENT FINDINGS: Adverse graft inflammation creates extreme resistance to the induction of donor-specific tolerance. Proinflammatory cytokines, when abundantly expressed within the graft and draining lymph nodes, prevent commitment of donor-activated T cells into graft-protective, T-regulatory phenotype, while fostering generation of donor-reactive Th1, Th2 or Th17 effector subsets. In addition, the inflammatory milieu may destabilize the program of both natural and induced Tregs, converting them into inflammatory, effector-like phenotypes. Therefore permanent, Treg-dependent acceptance of an allograft may not be achieved without limiting adverse tissue inflammation. SUMMARY: Balance of graft-protective regulatory and graft-destructive effector T cells largely depends on the balance of proinflammatory and anti-inflammatory cytokines in the milieu, in which donor-directed T-cell response occurs. In the absence of proinflammatory cytokines, the constitutive expression of TGF-beta may guide recipient T cells into a tissue-protective, pro-tolerant mode. Therefore, targeting adverse tissue inflammation may represent a powerful means to tilt antidonor immunity towards tolerance.
PURPOSE OF REVIEW: Inflammation of the allograft, occurring as a consequence of hypoxia and ischemia/reperfusion injury, adversely influences short-term and long-term transplant outcomes. Thus far, imbalance of tissue-protective Treg and tissue-destructive Th17 cells has been confirmed in a number of tissue-inflammatory states, including autoimmune disease. Hence, benefits of tilting Treg-Th17 equilibrium toward dominance of Tregs may promote transplant tolerance. RECENT FINDINGS: Adverse graft inflammation creates extreme resistance to the induction of donor-specific tolerance. Proinflammatory cytokines, when abundantly expressed within the graft and draining lymph nodes, prevent commitment of donor-activated T cells into graft-protective, T-regulatory phenotype, while fostering generation of donor-reactive Th1, Th2 or Th17 effector subsets. In addition, the inflammatory milieu may destabilize the program of both natural and induced Tregs, converting them into inflammatory, effector-like phenotypes. Therefore permanent, Treg-dependent acceptance of an allograft may not be achieved without limiting adverse tissue inflammation. SUMMARY: Balance of graft-protective regulatory and graft-destructive effector T cells largely depends on the balance of proinflammatory and anti-inflammatory cytokines in the milieu, in which donor-directed T-cell response occurs. In the absence of proinflammatory cytokines, the constitutive expression of TGF-beta may guide recipient T cells into a tissue-protective, pro-tolerant mode. Therefore, targeting adverse tissue inflammation may represent a powerful means to tilt antidonor immunity towards tolerance.
Authors: Young Rae Ji; Hei Jung Kim; Ki Beom Bae; Sanggyu Lee; Myoung Ok Kim; Zae Young Ryoo Journal: J Biol Chem Date: 2015-04-06 Impact factor: 5.157
Authors: Roberto Gedaly; Felice De Stefano; Lilia Turcios; Marita Hill; Giovanna Hidalgo; Mihail I Mitov; Michael C Alstott; D Allan Butterfield; Hunter C Mitchell; Jeremy Hart; Ahmad Al-Attar; Chester D Jennings; Francesc Marti Journal: Transplantation Date: 2019-04 Impact factor: 4.939