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Obaculactone suppresses Th1 effector cell function through down-regulation of T-bet and prolongs skin graft survival in mice

Authors
Publisher
Elsevier Inc.
Publication Date
Volume
80
Issue
2
Identifiers
DOI: 10.1016/j.bcp.2010.03.028
Keywords
  • Obaculactone
  • Allorejection
  • Th1 Effector Cell
  • T-Bet
  • Treg Cell
Disciplines
  • Medicine

Abstract

Abstract Allograft rejection is a predominantly Th1 immune response. In this study, we showed that obaculactone, a natural compound derived from citrus fruit, prolonged skin graft survival in mice when treated after but not before transplantation. Furthermore, obaculactone inhibited alloantigen-specific production of Th1 cytokine IFN-γ as well as proinflammatory cytokine IL-2, TNFα and IL-6. In parallel, IL-10 production was markedly up-regulated. Obaculactone significantly enhanced the percentage of CD4 +CD25 +Foxp3 + Treg cells in the CD4 + splenocytes without any effect on their inhibitory function. In vitro and in vivo tests showed obaculactone down-regulated T-bet expression in Th1 effector cells. Taken together, the unique immunomodulatory properties might qualify obaculactone as a putative, therapeutic compound for the treatment of Th1-driven diseases, including transplant rejection.

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