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Targeting of the hNC16A collagen domain to dendritic cells induces tolerance to human type XVII collagen

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 tole...

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Bibliographic Details
Main Authors: Ettinger, Monika (Author) , Mahnke, Karsten (Author)
Format: Article (Journal) Editorial
Language:English
Published: May 2012
In: Experimental dermatology
Year: 2012, Volume: 21, Issue: 5, Pages: 395-398
ISSN:1600-0625
DOI:10.1111/j.1600-0625.2012.01474.x
Online Access:Verlag, Pay-per-use, Volltext: http://dx.doi.org/10.1111/j.1600-0625.2012.01474.x
Verlag, Pay-per-use, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0625.2012.01474.x
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Author Notes:Monika Ettinger, Iris K. Gratz, Christina Gruber, Cornelia Hauser‐Kronberger, Theron S. Johnson, Karsten Mahnke, Josef Thalhamer, Helmut Hintner, Doris Peckl‐Schmid and Johann W. Bauer

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520 |a 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. 
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