title: Mechanisms and mediators of inflammation: potential models for skin rejection and targeted therapy in vascularized composite allotransplantation.
abstract: Vascularized composite allotransplantation (VCA) is an effective treatment option for patients suffering from limb loss or severe disfigurement. However, postoperative courses of VCA recipients have been complicated by skin rejection, and long-term immunosuppression remains a necessity for allograft survival. To widen the scope of this quality-of-life improving procedure minimization of immunosuppression in order to limit risks and side effects is needed. In some aspects, the molecular mechanisms and dynamics of skin allograft rejection seem similar to inflammatory skin conditions. T cells are key players in skin rejection and are recruited to the skin via activation of adhesion molecules, cytokines, and chemokines. Blocking these molecules has not only shown success in the treatment of inflammatory dermatoses, but also prolonged graft survival in various models of solid organ transplantation. In addition to T cell recruitment, ectopic lymphoid structures within the allograft associated with chronic rejection in solid organ transplantation might contribute to the strong alloimmune response towards the skin. Selectively targeting the molecules involved offers exciting novel therapeutic options in the prevention and treatment of skin rejection after VCA.
authors.affiliation: Center for Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Innsbruck Medical University, Anichstr. 35, A-6020 Innsbruck, Austria.
authors.forename: Theresa
authors.initials: T
authors.lastname: Hautz
authors.forename: Dolores
authors.initials: D
authors.lastname: Wolfram
authors.forename: Johanna
authors.initials: J
authors.lastname: Grahammer
authors.forename: Ravi
authors.initials: R
authors.lastname: Starzl
authors.forename: Christoph
authors.initials: C
authors.lastname: Krapf
authors.forename: Johann
authors.initials: J
authors.lastname: Pratschke
authors.forename: W P Andrew
authors.initials: WP
authors.lastname: Lee
authors.forename: Gerald
authors.initials: G
authors.lastname: Brandacher
authors.forename: Stefan
authors.initials: S
authors.lastname: Schneeberger
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000276:immunology* / Q000628:therapy*; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D012867:Skin / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D018836:Inflammation Mediators