Langerhans cells: critical regulators of skin immunity?

Langerhans cells (LC) are members of the heterogenous family of professional antigen presenting dendritic cells (DC). They are identified by the C-type lectin receptor Langerin and form a contiguous network in the epidermis. Consequently, LC are an integral part of the skin barrier to the environment and were considered to be critical inducers of skin immunity, whereas dermal DC were largely overlooked. However, with the identification of a distinct subset of Langerin expressing dermal DC, the situation in the skin has become more complex and the relative contribution of the different cutaneous DC populations in balancing immunity and tolerance has become a matter of active debate. Here, we briefly review the classical paradigm and recent challenges of LC function, before focusing on advances concerning their role in contact hypersensitivity and ultraviolet radiation-induced immunosuppression obtained with in vivo LC ablation models. We then discuss novel LC/DC-specific gene targeting approaches currently used to dissect the role of the regulatory cytokines transforming growth factor-beta and interleukin-10 to govern LC and DC function in vivo. This second generation of LC-specific genetically engineered mice will considerably extend our understanding of the molecular control of LC function in regulating skin immunity and tolerance in the near future.