Nature Immunology
3, 1135 - 1141 (2002)
Published online: 4 November 2002; | doi:10.1038/ni852
There is a Corrigendum (January 2003) associated with this Article.
Langerhans cells renew in the skin throughout life under steady-state conditionsMiriam Merad1, Markus G. Manz1, 4, Holger Karsunky1, Amy Wagers1, Wendy Peters2, Israel Charo2, Irving L. Weissman1, Jason G. Cyster3
& Edgar G. Engleman11
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94304, USA. 2
Gladstone Institute of Cardiovascular Disease, Cardiovascular Research Institute and the Department of Medicine, University of California, San Francisco, CA, USA. 3
Department of Immunology and Microbiology, University of California San Francisco, CA, USA. 4
Present address: Institute for Research in Biomedicine (IRB), 6500 Bellinzona, Switzerland.
Correspondence should be addressed to Miriam Merad meradm@stanford.eduLangerhans cells (LCs) are bone marrow (BM)−derived epidermal dendritic cells (DCs) that represent a critical immunologic barrier to the external environment, but little is known about their life cycle. Here, we show that in lethally irradiated mice that had received BM transplants, LCs of host origin remained for at least 18 months, whereas DCs in other organs were almost completely replaced by donor cells within 2 months. In parabiotic mice with separate organs, but a shared blood circulation, there was no mixing of LCs. However, in skin exposed to ultraviolet light, LCs rapidly disappeared and were replaced by circulating LC precursors within 2 weeks. The recruitment of new LCs was dependent on their expression of the CCR2 chemokine receptor and on the secretion of CCR2-binding chemokines by inflamed skin. These data indicate that under steady-state conditions, LCs are maintained locally, but inflammatory changes in the skin result in their replacement by blood-borne LC progenitors.
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