Interleukin-17 Accelerates Allograft Rejection by Suppressing Regulatory T Cell Expansion

Abstract

Background-Interleukin-17 , which is predominantly produced by T helper 17 cells distinct from T helper 1 or T helper 2 cells, participates in the pathogenesis of infectious, autoimmune, and allergic disorders. However, the precise role in allograft rejection remains uncertain. In the present study, we investigated the role of IL-17 in acute allograft rejection using IL-17-deficient mice. Methods and Results-Donor hearts from FVB mice were heterotopically transplanted into either C57BL/6J-IL-17-deficient (IL-17

IL-17 Deficiency Attenuates Allograft Injury and Prolongs Survival in a Murine Model of Fully MHC-Mismatched Renal Allograft Transplantation

“…This is consistent with the findings reported in a murine cardiac allograft model (30). It is possible that IL-17 deficiency either enhanced Treg actions via removing the antagonistic effects of Th17 effector cells, or indirectly facilitating Tregmediated immune modulation via abrogating the actions of IL-17 on effector cells such as macrophages and dendritic …”

“…Cardiac allograft rejection and resistance to graft tolerance was mediated by Th17 effector cells even in the absence of a Th1 immune response (26)(27)(28). IL-17 was reported to promote the maturation of dendritic cell progenitors (29) and graft inflammation (30) in separate models of murine cardiac allograft rejection, thus suggesting its potential role in facilitating the acute rejection response. Increased expression of IL-17 mRNA and protein has been demonstrated during the early stages of renal allograft rejection in both humans (31,32) and animal models (33,34).…”

Th-17 Alloimmune Responses in Renal Allograft Biopsies From Recipients of Kidney Transplants Using Extended Criteria Donors During Acute T Cell–Mediated Rejection

“…However, high Foxp3 mRNA urine expression at the time of acute rejection after kidney allograft transplantation, especially in patients with reversible rejection, suggest that resident Tregs are able to control intragraft severity of alloimmune response (25). In cardiac and lung transplantation models, IL-17 deficiency is associated with high numbers of regulatory cells and prolonged graft survival (26) and activation of the Th17 pathway strongly promotes chronic rejection (27). In kidney transplantation, Th17 cells within the explanted kidney allograft are associated with rapidly progressing chronic rejection (28).…”

Role of interleukin-17A in early graft rejection after orthotopic lung transplantation in mice

“…Tregs are potent immunosuppressive cells that have been shown to prolong allograft survival (36). Inhibition of Tregs via increased IL-6 production may represent another pathway of rejection caused by IL-17, and this has been demonstrated previously in rodent heart graft rejection (37).…”