title: Galectin-9 significantly prolongs the survival of fully mismatched cardiac allografts in mice.
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.
authors.affiliation: Institute of Organ Transplantation Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Ministry of Health, Key Laboratory of Ministry of Education, Wuhan, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: He
authors.forename: Zemin
authors.initials: Z
authors.lastname: Fang
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.forename: Hongmin
authors.initials: H
authors.lastname: Zhou
authors.forename: Dunfeng
authors.initials: D
authors.lastname: Du
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Zhang
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
authors.forename: Jin
authors.initials: J
authors.lastname: Yuan
authors.forename: Zhonghua Klaus
authors.initials: ZK
authors.lastname: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D037161:Galectins / Q000235:genetics / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000235:genetics; D020381:Interleukin-17 / Q000235:genetics; D008024:Ligands; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D017931:DNA Primers; D037161:Galectins; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D020381:Interleukin-17; C105032:LGALS9 protein, human; D008024:Ligands; D008565:Membrane Proteins; D012333:RNA, Messenger; D011991:Receptors, Virus; D011994:Recombinant Proteins; C508186:galectin 9, mouse; D007371:Interferon-gamma