Dendritic cells and the assessment in vitro of skin sensitizing potential.

ABSTRACT

It is now well established that dendritic cells (DC) play pivotal roles in the initiation and orchestration of adaptive immune responses, including cutaneous immune responses to chemical allergens that drive the acquisition of skin sensitization. It is not unexpected, therefore, that a large number, and wide variety, of proposed approaches for the identification of skin sensitizing chemicals in vitro are based upon the use of cultured DC or DC-like cells. The use of DC in this context is legitimate. However, with our rapidly increasing understanding of the diversity of cutaneous DC with respect to both phenotype and function, it is timely now to review briefly the potential limitations and interpretive difficulties that are associated with the use of DC-based assays. Among the important considerations are the fact that chemical-induced changes in the characteristics and function of cultured DC will not necessarily reflect accurately the events that that support the development of skin sensitization in vivo. In addition, most DC-based assays are predicated on a view that cutaneous DC have as their primary function the initiation of adaptive immune responses. However, it is now appreciated that cutaneous DC, and in particular epidermal Langerhans cells (LC), may also play important immunoregulatory roles that serve to limit and contain skin immune responses. Notwithstanding these considerations there is reason to believe that at least some in vitro DC-based assays are of value, and indeed some are currently the subject of a formal validation process. However, it is appropriate that such assays are configured and interpreted carefully, and with an appreciation of the complexity of DC biology.