Human dendritic cell functional specialization in steady-state and inflammation

Abstract

Dendritic cells (DC) represent a heterogeneous population of antigen-presenting cells that are crucial in initiating and shaping immune responses. Although all DC are capable of antigen-uptake, processing, and presentation to T cells, DC subtypes differ in their origin, location, migration patterns, and specialized immunological roles. While in recent years, there have been rapid advances in understanding DC subset ontogeny, development, and function in mice, relatively little is known about the heterogeneity and functional specialization of human DC subsets, especially in tissues. In steady-state, DC progenitors deriving from the bone marrow give rise to lymphoid organ-resident DC and to migratory tissue DC that act as tissue sentinels. During inflammation additional DC and monocytes are recruited to the tissues where they are further activated and promote T helper cell subset polarization depending on the environment. In the current review, we will give an overview of the latest developments in human DC research both in steady-state and under inflammatory conditions. In this context, we review recent findings on DC subsets, DC-mediated cross-presentation, monocyte-DC relationships, inflammatory DC development, and DC-instructed T-cell polarization. Finally, we discuss the potential role of human DC in chronic inflammatory diseases.

Keywords: dendritic cells; functional specialization; humans; inflammation; inflammatory dendritic cells; monocytes; skin; subsets.

Figure 1

Monocyte and dendritic cell populations in human peripheral blood during steady-state conditions. Expression of markers commonly used to identify and discern these populations are indicated. Additionally, frequencies (%) of monocyte subsets within the monocyte pool and dendritic cells within the dendritic cell pool are specified.

Figure 2

Dendritic cell populations in human skin during steady-state conditions. Expression levels of markers commonly used to identify and discern these populations are indicated.

Figure 3

Dendritic cell populations in human skin during inflammatory conditions. Inflamed skin contains not only DC that were already present at steady-state (A), but also DC that migrated into the skin (B). Markers commonly used to identify these DC populations are indicated, as well as markers/function associated with specific inflammatory conditions of the skin. LC, Langerhans cell; Ps, psoriasis; AD, atopic dermatitis.