Nature Medicine
- 12, 1372 - 1379 (2006)
Published online: 3 December 2006; | doi:10.1038/nm1518
Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cellsKarin Loser1, 2, Annette Mehling1, Stefanie Loeser3, Jenny Apelt1, Annegret Kuhn4, Stephan Grabbe5, Thomas Schwarz6, Josef M Penninger3 & Stefan Beissert1, 21
Department of Dermatology, University of Münster, D-48149 Münster, Germany. 2
Interdisciplinary Center of Clinical Research (IZKF), University of Münster, D-48149 Münster, Germany. 3
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria. 4
Division for Immunogenetics, Tumor Immunology Program, German Cancer Research Center, D-69120 Heidelberg, Germany. 5
Department of Dermatology, University of Essen, D-45122 Essen, Germany. 6
Department of Dermatology, University of Kiel, D-24105 Kiel, Germany.
Correspondence should be addressed to Stefan Beissert beisser@uni-muenster.de 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- B (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.
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