Borges Thiago J, Lee Catherine A A, Mucciarone Kyla, Lima Karina, Lape Isadora T, Lima-Filho Mauricio, Ayoama Bruno, Kollar Branislav, Gassen Rodrigo B, Bonorino Cristina, Talbot Simon G, Pomahac Bohdan, Lian Christine G, Murphy George F, Riella Leonardo V
Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Am J Transplant. 2025 Aug;25(8):1621-1630. doi: 10.1016/j.ajt.2025.04.016. Epub 2025 Apr 24.
The skin is the most immunogenic tissue in transplantation and the most difficult tissue in which to induce immune modulation. Batf3-dependent type 1 conventional dendritic cells (cDC1s) are important in initiating rejection in murine skin transplantation. In humans, the CD141 cDC1 subset is the functional counterpart of the murine Batf3-dependent cDC1s. However, their contribution to the rejection of human skin allografts remains unknown. Using samples from human face and upper extremity transplant recipients, we demonstrated that CD141 cDC1s are increased and more activated in human skin grafts than native skin tissue from the same individual. Moreover, circulating and tissue CD141 cDC1s were elevated at rejection time points. Local modulation of graft CD141 cDC1s decreased HLA-DR expression and increased regulatory T cells, which correlated with a decreased presence of skin allogeneic T cells in a humanized transplantation model. Thus, CD141 cDC1s play an important role in rejecting human skin allografts, and their local modulation is a promising therapeutic approach.
