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Langerin Expressing Cells Promote Skin Immune Responses under Defined Conditions¹

Liangchun Wang^*, Laura S. Bursch^*, Adrien Kissenpfennig^2,, Bernard Malissen, Stephen C. Jameson^* and Kristin A. Hogquist^3,*

^* Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455; and Centre d’Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale U631, Centre National de la Recherche Scientifique Unité Mixte de Recherche 6102, Université de la Méditerrannée, Case 906, Marseille, France

There are conflicting data in the literature regarding the role of epidermal Langerhans cells (LC) in promoting skin immune responses. On one hand, LC can be extremely potent APCs in vitro, and are thought to be involved in contact hypersensitivity (CHS). On the other hand, it seems counterintuitive that a cell type continually exposed to pathogens at the organism’s barrier surfaces should readily trigger potent T cell responses. Indeed, LC depletion in one model led to enhanced contact hypersensitivity, suggesting they play a negative regulatory role. However, apparently similar LC depletion models did not show enhanced CHS, and in one case showed reduced CHS. In this study we found that acute depletion of mouse LC reduced CHS, but the timing of toxin administration was critical: toxin administration 3 days before priming did not impair CHS, whereas toxin administration 1 day before priming did. We also show that LC elimination reduced the T cell response to epicutaneous immunization with OVA protein Ag. However, this reduction was only observed when OVA was applied on the flank skin, and not on the ear. Additionally, peptide immunization was not blocked by depletion, regardless of the site. Finally we show that conditions which eliminate epidermal LC but spare other Langerin⁺ DC do not impair the epicutaneous immunization response to OVA. Overall, our results reconcile previous conflicting data in the literature, and suggest that Langerin⁺ cells do promote T cell responses to skin Ags, but only under defined conditions.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research was supported by National Institutes of Health Grants P01 AI35296 and UO1 70380 (to S.C.J. and K.A.H.). The generation and preliminary characterization of the LangEGFP and LangDTREGFP mice was supported by ANR ("DC in vivo" Project).

² Current address: Infection and Immunity Group, Centre for Cancer Research and Cell Biology, School of Biomedical Sciences, Queen’s University, Belfast, Ireland.

³ Address correspondence and reprint requests to Dr. Kristin A. Hogquist, Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455. E-mail address: hogqu001{at}umn.edu

⁴ Abbreviations used in this paper: LC, Langerhans cells; DC, dendritic cells; DTR, diphtheria toxin receptor; DT, diphtheria toxin; CHS, contact hypersensitivity; DNFB, dinitrofluorobenzene; TRITC, tetramethylrhodamine isothiocyanate; ECI, epicutaneous immunization.