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Cytokines in immune regulation
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Published online 16 May 2005. doi:10.1083/jcb.200501071
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 169, Number 4, 569-576
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 Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity

Clare L. Bennett1, Erwin van Rijn1, Steffen Jung3, Kayo Inaba4, Ralph M. Steinman5, Martien L. Kapsenberg1,2, and Björn E. Clausen1

1 Department of Cell Biology and Histology, Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, Netherlands
2 Department of Dermatology, Academic Medical Center (AMC), University of Amsterdam, 1105 AZ Amsterdam, Netherlands
3 Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel
4 Department of Animal Development and Physiology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan
5 Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021

Correspondence to Björn E. Clausen: b.e.clausen{at}amc.uva.nl


Abstract
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.

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.


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