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- Title
Targeting of the hNC16A collagen domain to dendritic cells induces tolerance to human type XVII collagen.
- Authors
Ettinger, Monika; Gratz, Iris K.; Gruber, Christina; Hauser-Kronberger, Cornelia; Johnson, Theron S.; Mahnke, Karsten; Thalhamer, Josef; Hintner, Helmut; Peckl-Schmid, Doris; Bauer, Johann W.
- Abstract
Antibodies, specific to murine DEC205, can be used to target antigens to dendritic cells. The immunodominant domain of human type XVII collagen, hNC16A, was fused to this antibody (DEC-hNC16A) and was administered as expression plasmid by gene gun transfection with the aim of inducing tolerance to human type XVII collagen in a skin transplantation model. Mice transfected with DEC-hNC16A were challenged with skin grafts from transgenic mice engineered to express human type XVII collagen. Graft survival was either prolonged or grafts were accepted infinitely (33% and 16%, respectively) upon treatment with DEC-hNC16A while 100% of grafts were rejected in untreated controls. Graft acceptance was associated with the absence of a CD4+ infiltrate and a dense CD8+ T-cell infiltrate and was not strictly dependent on antibody production. Our results show that DEC-hNC16A targets dendritic cells in vivo leading to prolonged survival of transgenic skin grafts. This indicates that DEC205-targeting may be used for the induction of tolerance to skin antigens, which would increase the chances of successful skin gene therapy of epidermolysis bullosa patients.
- Subjects
EPIDERMOLYSIS bullosa; DENDRITIC cells; COLLAGEN; GENE therapy; SKIN grafting
- Publication
Experimental Dermatology, 2012, Vol 21, Issue 5, p395
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/j.1600-0625.2012.01474.x