Langerhans cells are strongly reduced in the skin of transgenic mice overexpressing follistatin in the epidermis.
Activins are members of the transforming growth factor-beta (TGF-beta) family and are important for skin morphogenesis and wound healing. TGF-beta1 is necessary for the population of the epidermis with Langerhans cells (LC). However, a role for activin in LC biology is not known. To address this question, we analyzed skin from transgenic mice overexpressing the activin antagonist follistatin in the epidermis. Using immunofluorescence, we observed a striking decrease in the number of LC in the epidermis of transgenic mice in comparison to wild-type mice. Nevertheless, these LC expressed normal levels of major histocompatibility complex (MHC)-class II and Langerin/ CD207 in situ. In explant cultures of whole ear skin the number of dendritic cells (DC), which migrated into the culture medium, was reduced. This reduction was even more pronounced in cultures of epidermal sheets. Virtually all emigrated cutaneous DC displayed typical morphology with cytoplasmic "veils", showed translocation of MHC-class II to the surface membrane, and expressed the maturation marker 2A1. Thus, cutaneous DC from transgenic mice seemed to mature normally. These results demonstrate that overexpression of follistatin in the epidermis affects LC trafficking but not maturation and suggest a novel role of the follistatin-binding partner activin in LC biology.
Stoitzner
Patrizia
P
Department of Dermatology, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria. Patrizia.Stoitzner@uibk.ac.at
Stössel
Hella
H
Wankell
Miriam
M
Hofer
Susanne
S
Heufler
Christine
C
Werner
Sabine
S
Romani
Nikolaus
N
D028341:Activins / Q000378:metabolism; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D038681:Follistatin / Q000235:genetics / Q000378:metabolism*; D005802:Genes, MHC Class II; D007801:Langerhans Cells / Q000166:cytology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D046509:Tissue Culture Techniques
D000954:Antigens, Surface; D015415:Biomarkers; C498497:Cd207 protein, mouse; D038681:Follistatin; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D028341:Activins