Cutaneous dendritic cells in the crossfire between innate and adaptive immunity

Abstract

Even though epidermal Langerhans’ cells (LCs) have been one of the most thoroughly studied dendritic cell (DC) types in humans and rodents, there are still large gaps in our knowledge as to their immunobiological role in skin. Instead of exhaustively reviewing all of what we know about LCs, this presentation will highlight some recent LC-related discoveries and emphasize several overlooked properties of these cells. In particular, it is essential to our understanding of cutaneous immunohomeostasis to dissect the relative contribution that LCs make as regards both innate, as well as adaptive, immune reactions in skin. As a part of this presentation we will advance the notion that professional antigen-presenting cells (APCs) may be the primary cell type in which genetically programmed alterations become manifested as in chronic inflammatory diseases such as Crohn’s disease and psoriasis. Thus, we will propose a ‘paradigm shift’ away from regarding the T cell as the fundamentally important pathogenic cell type, and will more closely focus on genes and biochemical reaction pathways within DCs that may drive roque immune responses in skin. Of course it should be pointed out that much, if not all, of what is being mentioned about LCs could be equally applied to dermal DCs (DDCs). However, because of space constraints the primary emphasis will be centered on LCs rather than DDCs. Before delving into LC biology, a brief review of innate and adaptive immunity will be made. First, it should be emphasized that it is somewhat artificial to separate innate and adaptive immune reactions, because they do not operate as separate or parallel systems [1,2]. Rather, they represent a single highly integrated biological system designed to respond to infectious insults in a complementary fashion. The cutaneous innate immune response is rapid, providing an initial line of defense against microorganisms, is largely antigen nonspecific, and lacks immunological memory. Cellular constituents of the innate immune system in skin include keratinocytes, DCs, macrophages, natural killer (NK) cells, and neutrophils [3]. Adaptive immunity, in contrast, is delayed in onset, is antigen specific, and involves a recall response. It is critical that a proper balance between innate and adaptive responses be maintained, because if the innate response is inadequate septic shock may result from a cutaneous bacterial infection. On the other hand, an exaggerated innate response may yield a chronic autoimmune inflammatory-type response. More details regarding these scenarios will be provided later in the text. * Tel.: /1-708-327-3241; fax: /1-708-327-3239 E-mail address: bnickol@lumc.edu (B.J. Nickoloff). Journal of Dermatological Science 29 (2002) 159 /165