title: Alteration of innate immunity by donor IL-6 deficiency in a presensitized heart transplant model.
abstract: Engraftment of IL-6 deficient donor into wild-type recipient could significantly improve allograft survival through T cell lineage particularly regulatory T cells (Tregs) in non-sensitized transplant host. However, its effect on innate immune responses remains uncertain. Our data revealed that donor IL-6 deficiency significantly increased infiltration of two subsets of MDSCs (CD11b+Gr1+myeloid-derived suppressor cells), CD11b+Gr1(-low) and CD11b+Gr1(-int) with strong immunosuppression activity in the transplanted graft. It resulted in a dramatic increase of CD11b+Gr1(-low) frequency and a significant decrease of the frequency of CD11b+Gr1(-high) and CD4-CD8-NK1.1+ cells in the recipient's spleen. Unexpectedly, donor IL-6 deficiency could not significantly reduce macrophage frequency irrespective of in the host's spleen or graft. Taken together, suppression of innate immune effector cells and enhanced activity of regulatory MDSCs contributed to tolerance induction by blockade of IL-6 signaling pathway. The unveiled novel mechanism of targeting IL-6 might shed light on clinical therapeutic application in preventing accelerated allograft rejection for those pre-sensitized transplant recipients.
authors.affiliation: Department of Surgery and Medicine, Transplant International Research Centre (TIRC), Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou City, People's Republic of China.
authors.forename: Fangmin
authors.initials: F
authors.lastname: Ge
authors.forename: Shunzong
authors.initials: S
authors.lastname: Yuan
authors.forename: Lida
authors.initials: L
authors.lastname: Su
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Shen
authors.forename: Aibin
authors.initials: A
authors.lastname: He
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.forename: Weihua
authors.initials: W
authors.lastname: Gong
mesh_terms: D064591:Allografts / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D006085:Graft Survival; D016027:Heart Transplantation; D007113:Immunity, Innate / Q000235:genetics*; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000172:deficiency*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014181:Transplantation Immunology / Q000235:genetics*
chemical_list: D039481:CD11b Antigen; D015850:Interleukin-6