Human type 1 conventional dendritic cells contribute to skin transplant rejection
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.
Authors
- Thiago J. Borges (ORCID: https://orcid.org/0000-0002-6554-0169)
- Karina Lima (ORCID: https://orcid.org/0000-0003-2478-1182)
- Bohdan Pomahač (ORCID: https://orcid.org/0000-0003-3703-8240)
- Rodrigo Benedetti Gassen (ORCID: https://orcid.org/0000-0003-0513-1555)
- Simon G. Talbot (ORCID: https://orcid.org/0000-0002-6092-7401)
- Mauricio Lima-Filho (ORCID: https://orcid.org/0000-0001-8944-3542)
- Cristina Bonorino (ORCID: https://orcid.org/0000-0003-2755-3978)
- George J. Murphy (ORCID: https://orcid.org/0000-0003-3464-793X)
- Branislav Kollár (ORCID: https://orcid.org/0000-0001-6668-7798)
- John Y. Choi (ORCID: https://orcid.org/0000-0002-9299-3921)
- Isadora T. Lape
- Kyla Mucciarone (ORCID: https://orcid.org/0000-0003-3755-2370)
- Christine G. Lian (ORCID: https://orcid.org/0000-0003-4626-1612)
- Catherine Lee (ORCID: https://orcid.org/0000-0001-8525-9342)
- Bruno Ayoama
Institutions
- Brigham and Women's Hospital (US)
- Yale New Haven Hospital (US)
- Universidade Federal de Ciências da Saúde de Porto Alegre (BR)
- Harvard University (US)
- University of Freiburg (DE)
- University Medical Center Freiburg (DE)
- Massachusetts General Hospital (US)
- Center for Systems Biology (US)
Publication Details
- Journal
- American Journal of Transplantation
- Published
- 2025-04-24
- DOI
- https://doi.org/10.1016/j.ajt.2025.04.016
- Citations
- 5
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 3.99