Involvement of hyaluronan in epidermal Langerhans cell maturation and migration in vivo

Langerhans cells (LC) normally reside in the epidermis, where they constantly monitor the integrity of this microenvironment. Skin exposure to reactive haptens or other pro-inflammatory stimuli triggers LC migration to the draining lymph nodes, where they function as potent antigen presenting cells. At the same time, migratory LC exhibit features of mature dendritic cells.

The purpose of this study was to determine the potential role(s) of hyaluronan (HA) in the process of LC maturation.

Using a recently described inhibitor of HA, termed 'Pep-1', we assessed the kinetics of LC migration and maturation in mice. Migration was determined by assessing LC density in epidermal sheets after hapten application. Epidermal LC maturation was evaluated by cell morphology, surface expression of CD86 and allogeneic mixed lymphocyte reactions.

Local injections of Pep-1 prevented LC migration from hapten-painted skin almost completely in the first 24 h. On the other hand, LC began to emigrate from the epidermis at 48 h, indicating that Pep-1 simply delayed LC migration by approximately 24 h. Locally injected Pep-1 inhibited hapten-induced LC maturation at 24 h as assessed by morphological changes, CD86 expression levels, and T cell-stimulatory potentials. Strikingly, all maturational changes became detectable at 48 h.

Pep-1 inhibits LC migration and maturation with the same kinetics, presumably reflecting close association of the two events. Moreover, our results suggest dual functionality of HA to facilitate LC migration and maturation, the two critical events for the initiation of adaptive immune responses in the skin.