Epidermal Langerhans cell-deficient mice develop enhanced contact hypersensitivity

Daniel H Kaplan, Mathew C. Jenison, Sem Saeland, Warren D. Shlomchik, Mark J. Shlomchik

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482 Scopus citations

Abstract

Epidermal Langerhans cells (LCs), a distinct skin-resident dendritic cell population, acquire antigen in the skin and migrate to draining lymph nodes where they are thought to initiate adaptive immune responses. To examine the functional requirement of LCs in skin immunity, we generated BAC transgenic mice in which the regulatory elements from human Langerin were used to drive expression of diphtheria toxin. The resulting mice have a constitutive and durable absence of epidermal LCs but are otherwise intact. Unexpectedly, we found that contact hypersensitivity (CHS) was amplified rather than abrogated in the absence of LCs. Moreover, we showed that LCs act during the priming and not the effector phase. Thus, LCs not only were dispensable for CHS, but they served to regulate the response, a previously unappreciated function.

Original languageEnglish (US)
Pages (from-to)611-620
Number of pages10
JournalImmunity
Volume23
Issue number6
DOIs
StatePublished - Dec 2005

Bibliographical note

Funding Information:
We thank Drs. Robert Tigelaar, Britt Anderson, and Phil Askenase for critical reading of the manuscript and many helpful discussions. M.J.S. would like to thank Michel Nussenzweig and members of his lab for generously teaching him the technique of homologous recombination in BACs. We thank Dr. Ian Maxwell for providing the diphtheria toxin construct. We also thank Michelle Horniak, Terrence Hunt, and the Yale Animal Resources Center for outstanding animal husbandry that made these studies possible. Supported by NIH grants R01-AR44077 and R01-HL66279 to M.J.S. and K08-AR651092 and K08-AR51092 to D.H.K. This work was also supported by the Dermatology Foundation.

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