Abstract
Langerhans cells (LC) are a unique population of tissue-resident macrophages that form a network of cells across the epidermis of the skin, but which have the ability to migrate from the epidermis to draining lymph nodes (LN). Their location at the skin barrier suggests a key role as immune sentinels. However, despite decades of research, the role of LC in skin immunity is unclear; ablation of LC results in neither fatal susceptibility to skin infection nor overt autoimmunity due to lack of immune regulation. Our understanding of immune processes has traditionally been centered on secondary lymphoid organs as sites of lymphocyte priming and differentiation, which is exemplified by LC, initially defined as a paradigm for tissue dendritic cells that migrate to draining LN on maturation. But, more recently, an awareness of the importance of the tissue environment in shaping effector immunity has emerged. In this mini-review, we discuss whether our lack of understanding of LC function stems from our lymph node-centric view of these cells, and question whether a focus on LC as immune regulators in situ in the skin may reveal clearer answers about their function in cutaneous immunology.
Highlights
Langerhans cells (LC) are a unique population of mononuclear phagocytes that are seeded from common macrophage precursors in the skin epidermis before birth [1]
Immunologists have focused on secondary lymphoid organs as the center of T cell immunity, assuming that instructions given during the priming of naïve T cells by migratory and resident dendritic cells (DC) were sufficient for differentiation and effector function by T cells recruited to peripheral sites of tissue injury
Despite sharing an origin with other tissue-resident macrophages, differentiation of LC is associated with the acquisition of DC-like functions, namely the ability to migrate to skin-draining lymph nodes (LN) and interact with naïve T cells
Summary
Langerhans cells (LC) are a unique population of mononuclear phagocytes that are seeded from common macrophage precursors in the skin epidermis before birth [1] (and reviewed in this topic) They are highly conserved across vertebrate species [2, 3] and this, with their location at the interface with the environment, suggests the strategic importance of LC as immune sentinels at the skin barrier surface. Despite sharing an origin with other tissue-resident macrophages, differentiation of LC is associated with the acquisition of DC-like functions, namely the ability to migrate to skin-draining lymph nodes (LN) and interact with naïve T cells Observation of this property in the 1980s has dominated the field, and as a result, studies to define LC function in the skin have focused largely on their role as DC-like cells in priming T cell immunity [reviewed by Romani et al [5]]. To date, a consistent role for LC as primers of T cell immunity has not emerged
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