Langerhans cells (LC) form a unique subset of dendritic cells (DC) in the epidermis but so far their in vivo functions in skin immunity and tolerance could not be determined, in particular in relation to dermal DC (dDC). Here, we exploit a novel diphtheria toxin (DT) receptor (DTR)/DT-based system to achieve inducible ablation of LC without affecting the skin environment. Within 24 h after intra-peritoneal injection of DT into Langerin-DTR mice LC are completely depleted from the epidermis and only begin to return 4 wk later. LC deletion occurs by apoptosis in the absence of inflammation and, in particular, the dDC compartment is not affected. In LC-depleted mice contact hypersensitivity (CHS) responses are significantly decreased, although ear swelling still occurs indicating that dDC can mediate CHS when necessary. Our results establish Langerin-DTR mice as a unique tool to study LC function in the steady state and to explore their relative importance compared with dDC in orchestrating skin immunity and tolerance.
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23 May 2005
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May 16 2005
Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity
Clare L. Bennett,
Clare L. Bennett
1Department of Cell Biology and Histology, Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, Netherlands
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Erwin van Rijn,
Erwin van Rijn
1Department of Cell Biology and Histology, Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, Netherlands
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Steffen Jung,
Steffen Jung
3Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
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Kayo Inaba,
Kayo Inaba
4Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan
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Ralph M. Steinman,
Ralph M. Steinman
5Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
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Martien L. Kapsenberg,
Martien L. Kapsenberg
1Department of Cell Biology and Histology, Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, Netherlands
2Department of Dermatology, Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, Netherlands
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Björn E. Clausen
Björn E. Clausen
1Department of Cell Biology and Histology, Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, Netherlands
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Clare L. Bennett
1Department of Cell Biology and Histology, Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, Netherlands
Erwin van Rijn
1Department of Cell Biology and Histology, Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, Netherlands
Steffen Jung
3Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
Kayo Inaba
4Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan
Ralph M. Steinman
5Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021
Martien L. Kapsenberg
1Department of Cell Biology and Histology, Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, Netherlands
2Department of Dermatology, Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, Netherlands
Björn E. Clausen
1Department of Cell Biology and Histology, Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, Netherlands
Correspondence to Björn E. Clausen: [email protected]
Abbreviations used in this paper: CHS, contact hypersensitivity; DC, dendritic cells; dDC, dermal DC; DT, diphtheria toxin; DTR, DT receptor; ES, embryonic stem; LC, Langerhans cells; LN, lymph node; MHCII, major histocompatability complex class II; TNCB, trinitrochlorobenzene; wt, wild-type.
Received:
January 14 2005
Accepted:
April 13 2005
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2005
J Cell Biol (2005) 169 (4): 569–576.
Article history
Received:
January 14 2005
Accepted:
April 13 2005
Citation
Clare L. Bennett, Erwin van Rijn, Steffen Jung, Kayo Inaba, Ralph M. Steinman, Martien L. Kapsenberg, Björn E. Clausen; Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity . J Cell Biol 23 May 2005; 169 (4): 569–576. doi: https://doi.org/10.1083/jcb.200501071
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