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Galectin-9 Significantly Prolongs the Survival of Fully Mismatched Cardiac Allografts in Mice

Galectin-9 Significantly Prolongs the Survival of Fully Mismatched Cardiac Allografts in Mice

Wentao He, Zemin Fang, Feng Wang, Ke Wu, Yi Xu, Hongmin Zhou, Dunfeng Du, Ying Gao, Wei-Na Zhang, Toshiro Niki, Mitsuomi Hirashima, Jin Yuan, Zhonghua Klaus Chen

Transplantation. 2009 Sep 27;88(6):782-90.

PMID: 19920777

Abstract:

Background:
The involvement of T-cell immunoglobulin mucin-3 (Tim-3) in the regulation of solid organ transplantation rejection is largely unknown. We used galectin-9 (Tim-3 ligand) to evaluate the effect and mechanisms of Tim-3/galectin-9 pathway in an allogeneic heart transplant model.
Methods:
The murine cardiac transplant model from BALB/c (H-2d) to C57BL/6 (H-2b) was built. The recipients were administered with galectin-9 for 7 days from day 1 or day 3 posttransplant. The complete cessation of cardiac contractility was defined as the observation endpoint. The effect of galectin-9 on cell proliferation was assessed by mixed lymphocyte reaction. Histology and immunohistochemistry were performed to estimate the severity of rejection. The phenotype and cytokine profile of lymphocytes were analyzed by flow cytometry.
Results:
In vitro, galectin-9 suppressed the proliferation of lymphocytes mixed lymphocyte reactions in a dose- and beta-galactoside-dependent manner. In vivo, galectin-9 treatment from day 1 to day 3 posttransplant achieved similar survival time of grafts (median survival time, 22.7+/-1.2 vs. 23.0+/-1.0 days). The prolonged survival time was associated with reduced infiltration of CD4 and CD8 lymphocytes in allografts. Furthermore, the intragraft transcriptional profiling in galectin-9-treated group showed reduction of IFN-gamma and IL-17 mRNA but elevation of Ebi-3 and galectin-9 mRNA. Flow cytometry analysis indicated that galectin-9 treatment reduced the ratio of T helper (Th) 1 and Th17 cells in the draining lymph nodes and peripheral blood.
Conclusions:
A short-course administration of galectin-9 significantly prolonged the survival of fully allogeneic cardiac allografts, which was associated with the suppression of Th1 and Th17 immune responses.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42413345	EBI-3 from mouse			Price

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