Cytokines and Langerhans cell mobilisation in mouse and man.
A critical event during the development of cutaneous immune responses, including those provoked by contact allergens, is the mobilisation of epidermal Langerhans cells (LC). These cells act as sentinels of the immune system in the skin, responding to a variety of local insults with migration and delivery of potentially foreign signals to draining lymph nodes. Experimental studies have revealed that the regulation of mobilisation and migration of LC display striking similarities in man and mouse. In both species it has been found that the successful induction of migration requires that LC receive (at least) 2 independent cytokine signals; provided by tumour necrosis factor-alpha (TNF-alpha) and interleukin 1beta. In addition, a similar heterogeneity in man and mouse is apparent with regard to the fraction of LC responding rapidly to mobilisation signals, with the same proportion of cells (20%-30%) being stimulated to migrate in each case. Other similarities exist between mice and humans with respect to LC function, including an age-related decrement in both LC frequency and responsiveness to TNF-alpha. Collectively these studies demonstrate that the mouse provides a valuable experimental surrogate for the human skin immune system, particularly with respect to LC biology, and suggest that it is possible to perform extrapolations between species with some confidence.