• Radhika Chadha, David A Leonard, Josef M Kurtz, and Curtis L Cetrulo.
• 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.
• Curr Opin Organ Transplant. 2014 Dec 1;19(6):566-72.

Purpose Of ReviewVascularized 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.Recent FindingsThere 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.SummaryMost 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.

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