Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells.
Regulatory CD4(+)CD25(+) T cells are important in suppressing immune responses. The requirements for the maintenance of peripheral CD4(+)CD25(+) T cells remain incompletely understood. Receptor activator of NF-kappaB (RANK) and its ligand (RANKL; also known as CD254, OPGL and TRANCE) are key regulators of bone remodeling, mammary gland formation, lymph node development and T-cell/dendritic cell communication. Here we report that RANKL is expressed in keratinocytes of the inflamed skin. RANKL overexpression in keratinocytes resulted in functional alterations of epidermal dendritic cells and systemic increases of regulatory CD4(+)CD25(+) T cells. Thus, epidermal RANKL expression can change dendritic cell functions to maintain the number of peripheral CD4(+)CD25(+) regulatory T cells. Epidermal RANKL mediated ultraviolet-induced immunosuppression and overexpression of epidermal RANKL suppressed allergic contact hypersensitivity responses and the development of systemic autoimmunity. Therefore, environmental stimuli at the skin can rewire the local and systemic immune system by means of RANKL.
Loser
Karin
K
Department of Dermatology, University of Münster, D-48149 Münster, Germany.
Mehling
Annette
A
Loeser
Stefanie
S
Apelt
Jenny
J
Kuhn
Annegret
A
Grabbe
Stephan
S
Schwarz
Thomas
T
Penninger
Josef M
JM
Beissert
Stefan
S
D000818:Animals; D015551:Autoimmunity; D002452:Cell Count; D003713:Dendritic Cells / Q000502:physiology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000502:physiology*; D007108:Immune Tolerance / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*; D014466:Ultraviolet Rays
D053245:RANK Ligand