Dermal mononuclear phagocytes

In immune responses of the skin, the connective
tissue environment of the dermis plays a decisive role.
Large numbers of resident mononuclear phagocytes
are located here and these are thought to be crucial
for the initiation and regulation of such responses.
Surprisingly, the characterization of dermal
mononuclear phagocytes, often distinguished as
macrophages and dendritic cells (DC), has been
limited compared to those in other immune organs
and to their Langerhans cell counterparts in the
epidermis. This is likely explained by the difficulty to
obtain dermal cells in large quantity. In this chapter,
we will provide an overview of the current insights on
dermal mononuclear phagocytes, using the different
technical approaches to study these cells as a guideline. For practical purposes
we will focus primarily on the steady-state situation and discuss this for human
and mouse skin. In situ analysis using skin sections has indicated that
mononuclear phagocytes represent a remarkably large proportion of nucleated
cells in the dermis, comprising multiple, phenotypically distinct subsets. Using
skin explant cultures or freshly isolated cells from dermal tissue, single cells can
be obtained. These approaches confirm the extensive heterogeneity of the dermal
mononuclear phagocytes. Interpreting the available data, we propose that a
developmental relationship may exist between the major subsets. While the cells
migrate upwards from the deeper layers in the dermis they mature and change
from endocytic macrophage-like cells to cells with an immunostimulatory DC
phenotype, which may leave the dermis via afferent lymphatics to interact with
the immune system in skin-draining lymph nodes.