Galectin-1 prolongs survival of mouse liver allografts from Flt3L-pretreated donors.
Liver allografts are spontaneously accepted across MHC barriers in mice. The mechanisms underlying this phenomenon remain poorly understood. Galectin-1, an endogenous lectin expressed in lymphoid organs, plays a vital role in maintaining central and peripheral tolerance. This study was to investigate the role of galectin-1 in spontaneous tolerance of liver allografts in mice, and to evaluate the therapeutic effects of galectin-1 on liver allograft rejection induced by donor Flt3L pretreatment. Blockade of the galectin-1 pathway via neutralizing antigalectin-1 mAb did not affect survival of the liver allografts from B6 donors into C3H recipients. Administration of rGal-1 significantly prolonged survival of liver allografts from Flt3L-pretreated donors and ameliorated Flt3L-triggered liver allograft rejection. This effect was associated with increased apoptosis of T cells in both allografts and spleens, decreased frequencies of Th1 and Th17 cells, decreased expression of Th1-associated cytokines (IL-12, IL-2 and IFN-γ), Th17-associated cytokines (IL-23 and IL-17) and granzyme B, in parallel with selectively increased IL-10 expression in liver allografts. In vitro, galectin-1 inhibited Flt3L-differentiated DC-mediated proliferation of allo-CD4(+)  T cells and production of IFN-γ and IL-17. These data provide new evidence of the potential regulatory effects of galectin-1 in alloimmune responses in a murine model of liver transplantation.
Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Y
Y
Ye
S
S
Yan
G
G
Jiang
L
L
Zhou
H
H
Xie
X
X
Xie
X
X
Yu
Y
Y
Ding
J
J
Tian
Y
Y
Dai
S
S
Zheng
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000502:physiology*; D007108:Immune Tolerance; D007124:Immunoenzyme Techniques; D008107:Liver Diseases / Q000276:immunology / Q000401:mortality* / Q000628:therapy; D016031:Liver Transplantation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics / Q000378:metabolism*
D037483:Galectin 1; D012333:RNA, Messenger; C497971:Flt3 protein, mouse; D051941:fms-Like Tyrosine Kinase 3