Langerhans Cells and How Skin Pathology Reshapes the Local Immune Environment

The skin forms an interface between the body and the external world. It acts as a physical barrier, but also contains a complex network of immune cells that co-operate to maintain a homeostasis in the presence of innocuous challenges, whilst remaining poised to respond to infections that enter the skin. The most external layer of the skin is the epidermis, composed of layers of differentiating keratinocytes, interspersed by immune cells. The healthy epidermis contains a single population of mononuclear cells known as Langerhans cells (LC). These are a unique population of antigen presenting cells that are seeded in the skin before birth and persist throughout life, without contribution from bone marrow precursors. It is still not entirely clear what LC do, but current consensus is that in the absence of infection they are important in the maintenance of immune regulation in the skin. However, we have recently shown that under conditions of skin pathology caused by GVHD, LC are subverted to drive tissue destruction by T cells. Tissue destruction leads to loss of the resident LC network and replacement by bone marrow-derived cells, including monocytes. This re-shaping of the LC network may have important implications for the continued maintenance of a homeostatic environment in the skin.

Communication between keratinocytes and immune cells regulates the healthy skin environment. We have shown that homeostatic regulators of epidermal keratinocytes, such as Notch signalling, play critical functions in the recruitment of immune cells required for the healing of acute wounds. Skin pathology due to disease or wounding causes dysregulation of these homeostatic regulators with long-term implications for the local immune environment.

This collection of reviews aims to introduce to readers our current thinking on the development and function of LC, with a focus on how pathology in the skin disturbs the finally regulated environment. We will present this understanding in the context of the broader impact on how trauma due to disease or wounding alters homeostatic signalling in the skin, and may ultimately permanently reshape the epidermal niche.