Epidermal Langerhans cells tune skin reactivity to contact allergens

Allergic contact dermatitis is a common disorder that has fascinated dermatologists and immunologists for decades. Extensive studies of contact sensitivity reactions in mice established a mechanistic paradigm that has been revisited in recent years, and the involvement of Langerhans cells (LCs), a population of epidermal dendritic cells, in immune responses to epicutaneously applied antigens has been questioned. In this issue of the JCI, Gomez de Agüero et al. describe an elegant series of experiments that implicate LCs in tolerance induction, positioning these cells as key regulators of immunologic barrier function.