TY - JOUR
T1 - Wnt signaling influences the development of murine epidermal langerhans cells
AU - Becker, Maria R.
AU - Choi, Yeon S.
AU - Millar, Sarah E.
AU - Udey, Mark C.
N1 - Funding Information:
We thank Dr William Telford for his advice and assistance with flow and laser scanning cytometer-related experiments. We also thank Jay Linton, Michael Lu, and Dr Sei-ichiro Motegi for advice and assistance with other experimental procedures. This work was supported by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, The National Institutes of Health encompasses the preceding items (program, center, institute).
PY - 2011/9
Y1 - 2011/9
N2 - Langerhans cells (LCs) are distinct dendritic cells (DCs) that populate stratified squamous epithelia. Despite extensive studies, our understanding of LC development is incomplete. Transforming growth factor Β1 (TGFΒ1) is required for LC development, but other epidermis-derived influences may also be important. Recently, EpCAM (CD326) has been identified as a cell surface protein discriminating LCs from Langerin dermal DCs and other DCs in the skin. EpCAM is a known transcriptional target of the Wnt signaling pathway. We hypothesized that intraepidermal Wnt signaling might influence LC development. Addition of Wnt3A into cultures of bone-marrow-derived cells in combination with TGFΒ1, GM-CSF, and M-CSF resulted in increased (33%; P0.05) accumulation of EpCAM DCs. In contrast, addition of the Wnt antagonist dickkopf-related protein 1 (Dkk1) decreased the number of EpCAM DCs (21%; P0.05). We used K14-KRM1; K5-rtTA; tetO-Dkk1 triple-transgenic and K5-rtTA; tetO-Dkk1 double-transgenic mice to test the in vivo relevance of our in vitro findings. Feeding doxycycline to nursing mothers induced expression of Dkk1 in the skin of transgenic pups, causing an obvious hair phenotype. Expression of Dkk1 reduced LC proliferation (40%; P0.01) on P7, decreased LC densities (26%; P0.05) on P14, and decreased EpCAM expression intensities on LCs as well (33%). In aggregate, these data suggest that Wnt signaling in skin influences LC development.
AB - Langerhans cells (LCs) are distinct dendritic cells (DCs) that populate stratified squamous epithelia. Despite extensive studies, our understanding of LC development is incomplete. Transforming growth factor Β1 (TGFΒ1) is required for LC development, but other epidermis-derived influences may also be important. Recently, EpCAM (CD326) has been identified as a cell surface protein discriminating LCs from Langerin dermal DCs and other DCs in the skin. EpCAM is a known transcriptional target of the Wnt signaling pathway. We hypothesized that intraepidermal Wnt signaling might influence LC development. Addition of Wnt3A into cultures of bone-marrow-derived cells in combination with TGFΒ1, GM-CSF, and M-CSF resulted in increased (33%; P0.05) accumulation of EpCAM DCs. In contrast, addition of the Wnt antagonist dickkopf-related protein 1 (Dkk1) decreased the number of EpCAM DCs (21%; P0.05). We used K14-KRM1; K5-rtTA; tetO-Dkk1 triple-transgenic and K5-rtTA; tetO-Dkk1 double-transgenic mice to test the in vivo relevance of our in vitro findings. Feeding doxycycline to nursing mothers induced expression of Dkk1 in the skin of transgenic pups, causing an obvious hair phenotype. Expression of Dkk1 reduced LC proliferation (40%; P0.01) on P7, decreased LC densities (26%; P0.05) on P14, and decreased EpCAM expression intensities on LCs as well (33%). In aggregate, these data suggest that Wnt signaling in skin influences LC development.
UR - http://www.scopus.com/inward/record.url?scp=80955181030&partnerID=8YFLogxK
U2 - 10.1038/jid.2011.131
DO - 10.1038/jid.2011.131
M3 - Article
AN - SCOPUS:80955181030
SN - 0022-202X
VL - 131
SP - 1861
EP - 1868
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 9
ER -