title: Adiponectin mediated MHC class II mismatched cardiac graft rejection in mice is IL-4 dependent.
abstract: BACKGROUND
  Adiponectin regulates glucose and fatty-acid metabolism but its role in chronic graft rejection mediated by Th2 cytokines remains ill-defined.
  
  
  RESULTS
  Wild type and adiponectin-null mice were used as graft recipients in mouse MHC class II disparate cardiac transplantation (bm12 toB6) and the graft rejection was monitored. In adiponectin-null mice we observed that the cellular infiltrate of eosinophils, CD4(+) and CD8(+) T cells was reduced in grafts compared to the controls as was collagen deposition and vessel occlusion. A similar outcome was observed for skin transplants except that neutrophil infiltration was increased. Low levels of IL-4 were detected in the grafts and serum. The effect of adiponectin signaling on IL-4 expression was further investigated. Treatment with AMPK and p38 MAPK inhibitors blocked adiponectin enhanced T cell proliferation in mixed lymphocyte reactions. Inhibition of AMPK reduced eosinophil infiltration in skin grafts in wild type recipients and in contrast AMPK activation increased eosinophils in adiponectin-null recipients. The addition of adiponectin increased IL-4 production by the T cell line EL4 with augmented nuclear GATA-3 and phospho-STAT6 expression which were suppressed by knockdown of adiponectin receptor 1 and 2.
  
  
  CONCLUSIONS
  Our results demonstrate a direct effect of adiponectin on IL-4 expression which contributes to Th2 cytokine mediated rejection in mouse MHC class II histoincompatible transplants. These results add to our understanding of the interrelationship of metabolism and immune regulation and raise the possibility that AMPK inhibitors may be beneficial in selected types of rejection.
authors.affiliation: Paediatric Surgery Division, Department of Surgery, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Daxu
authors.initials: D
authors.lastname: Li
authors.forename: Julia Y S
authors.initials: JY
authors.lastname: Tsang
authors.forename: Jiao
authors.initials: J
authors.lastname: Peng
authors.forename: Derek H H
authors.initials: DH
authors.lastname: Ho
authors.forename: Yee Kwan
authors.initials: YK
authors.lastname: Chan
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Vincent C H
authors.initials: VC
authors.lastname: Lui
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lamb
authors.forename: Paul K H
authors.initials: PK
authors.lastname: Tam
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism; D016027:Heart Transplantation / Q000276:immunology*; D015847:Interleukin-4 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016038:Skin Transplantation / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D052242:Adiponectin; D016207:Cytokines; D015847:Interleukin-4