title: The unique immunobiology of the skin: implications for tolerance of vascularized composite allografts.
abstract: OBJECTIVE
  Vascularized composite allograft (VCA) transplantation restores function and form following major soft tissue and musculoskeletal injury. Lifelong immunosuppression is necessary for graft function and survival but acute skin-targeted rejection episodes remain common. We review recent advances in skin immunobiology, emphasizing findings in clinical and experimental VCAs. We also highlight advances in immunotherapy and tolerance protocols with implications for the prevention of VCA rejection, and ultimately, induction of clinically applicable strategies for VCA tolerance.
  
  
  RESULTS
  There is now an increasing appreciation for the role of skin-specific mechanisms, including lymphoid neogenesis, in VCA rejection. In contrast, expression of the regulatory master-switch FOXP3 was demonstrated to be significantly upregulated in the skin of tolerant VCAs in large animal models compared with normal skin and rejecting controls.
  
  
  CONCLUSIONS
  Most VCA transplant centers continue to utilize antibody-mediated induction therapy and triple agent maintenance immunosuppression. Skin remains the primary target of rejection in VCAs, and current multicenter studies hope to elucidate the mechanisms involved. Proposed standardized procedures for skin biopsies, and diligent reporting of clinical data to the international registry, will be important to maximize the strength of these studies.
authors.affiliation: aUniversity of Oxford, Oxford, UK bTransplantation Biology Research Center cDivision of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA dDepartment of Plastic and Reconstructive Surgery Research, University of Manchester, Manchester, UK eDepartment of Biology, Emmanuel College, Boston, Massachusetts, USA.
authors.forename: Radhika
authors.initials: R
authors.lastname: Chadha
authors.forename: David A
authors.initials: DA
authors.lastname: Leonard
authors.forename: Josef M
authors.initials: JM
authors.lastname: Kurtz
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Cetrulo
mesh_terms: D000818:Animals; D064595:Composite Tissue Allografts; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D012867:Skin / Q000276:immunology*; D016038:Skin Transplantation
chemical_list: D007166:Immunosuppressive Agents