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Langerhans cells renew in the skin throughout life under steady-state conditions

Nature Immunology volume 3, pages 1135–1141 (2002)Cite this article

A Corrigendum to this article was published on 01 January 2003

Abstract

Langerhans 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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Figure 1: LC chimerism after congenic BM transplantation.
Figure 2: Origin of LCs in parabiotic mice.
Figure 3: Rate of LC proliferation in chimeric mice.
Figure 4: LC homeostasis during skin inflammation.
Figure 5: Role of CCR2 in the recruitment of circulating LC precursors to inflamed skin.
Figure 6: MCP chemokines and injured skin.

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Acknowledgements

We thank C. Benike for critical review of the manuscript, M. Katics for excellent animal care and D. Jones for formatting the manuscript. Supported by Ernst Schering Research Foundation (H. K.) and by grants from the National Institutes of Health (HL57443) and the Tobacco-Related Disease Research Program (9RT-0229) (to E. G. E.).

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  1. Markus G. Manz

    Present address: Institute for Research in Biomedicine (IRB), 6500, Bellinzona, Switzerland

Authors and Affiliations

  1. Department of Pathology, Stanford University School of Medicine, Stanford, 94304, CA, USA

    Miriam Merad, Markus G. Manz, Holger Karsunky, Amy Wagers, Irving L. Weissman & Edgar G. Engleman

  2. Cardiovascular Research Institute and the Department of Medicine, Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA, USA

    Wendy Peters & Israel Charo

  3. Department of Immunology and Microbiology, University of California, San Francisco, CA, USA

    Jason G. Cyster

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Merad, M., Manz, M., Karsunky, H. et al. Langerhans cells renew in the skin throughout life under steady-state conditions. Nat Immunol 3, 1135–1141 (2002). https://doi.org/10.1038/ni852

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