2025/04/24 by Thiago J. Borges, Catherine Lee, Kyla Mucciarone +12 · 1 voice
Immunology and Microbiology · Biochemistry, Genetics and Molecular Biology · #Immunotherapy and Immune Responses #T-cell and B-cell Immunology #RNA Interference and Gene Delivery
paper · doi:10.1016/j.ajt.2025.04.016
openalex publication_date 2025/04/24 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
<h2>Abstract</h2> 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<sup>+</sup> 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<sup>+</sup> cDC1s are increased and more activated in human skin grafts than native skin tissue from the same individual. Moreover, circulating and tissue CD141<sup>+</sup> cDC1s were elevated at rejection time points. Local modulation of graft CD141<sup>+</sup> 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<sup>+</sup> cDC1s play an important role in rejecting human skin allografts, and their local modulation is a promising therapeutic approach.