Obaculactone suppresses Th1 effector cell function through down-regulation of T-bet and prolongs skin graft survival in mice.
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-gamma as well as proinflammatory cytokine IL-2, TNFalpha 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.
Gong
Fangyuan
F
Nanjing University, China.
Shen
Yan
Y
Zhang
Qi
Q
Sun
Yang
Y
Tang
Jiayu
J
Tao
Feifei
F
Xu
Qiang
Q
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002957:Citrus / Q000737:chemistry*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D051858:Forkhead Transcription Factors / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D036701:Limonins / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology; D017452:Receptors, IgG / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D020825:T-Box Domain Proteins / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology; D014184:Transplantation, Homologous; D000098815:T-bet Transcription Factor
C418974:FOXP3 protein, human; C485700:Fcgr3 protein, mouse; D051858:Forkhead Transcription Factors; D036701:Limonins; D010936:Plant Extracts; D017452:Receptors, IgG; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma; C001546:limonin