Functional Diversity of Human Dendritic Cells

Abstract

At the crossroad between innate and adaptive immunity are the dendritic Cells (DCs), a "novel cell type." discovered in 1973 by Ralph Steinman. Although not entirely appreciated at first, it is clear that they play a critical role as specialized antigen-presenting cells and essential mediators in shaping immune reactivity and tolerance. Dendritic cells are now recognized as a heterogeneous group of cells in terms of cell-surface markers, anatomic location, and function adapted to protect against an array of pathogens and conditions. Importantly, these subsets are also unique to each species. While significant progress has been made on the identification and function of mouse DC subsets, much less is known about human cells. Here we review the fascinating biology of human skin DCs and describe tolerogenic principles that are critical in maintaining immune homeostasis and for controlling inflammation, as well as mechanisms that are fundamental to confer immunity. We surmise that these principles could be applied to DCs across organs, and could be harnessed for the treatment of various human autoimmune, inflammatory diseases, as well as cancer. Importantly, to leverage the relevance of basic research to the clinical setting, it is first necessary to determine the functional homology between mouse and human DCs. We discuss practical steps towards this aim.

S100A8 and S100A9 proteins are expressed by human corneal stromal dendritic cells

“…CD45 + /HLA-DR + /CD11c + DCs were detected within the corneal epithelium, but these superficially located DCs did not express A8 and A9 (figures 2 and 3), suggesting that a distinct subpopulation was discriminated by their S100 content. Recent studies describe DCs as heterogeneous, with functions dependent on their anatomical location and on the pathogens or conditions to which they are exposed; some DC subsets, such as those in the skin, contribute to tolerogenic mechanisms that maintain immune homeostasis 23. Interestingly, CD45 + /CD11c + DCs within the corneal epithelium exhibited a morphologically distinct dendritiform shape, whereas those located within the anterior limbal stroma appeared rounder 22.…”

A type of human skin dendritic cell marked by CD5 is associated with the development of inflammatory skin disease

“…DC subsets display different cell surface markers that afford each specific DC population different functions (2). Consequently, normal immunity and tolerance are dependent on a balance among the DC subsets.…”

Dendritic Cell–Derived IL-32α: A Novel Inhibitory Cytokine of NK Cell Function

“…Each one of these subsets produces unique cytokines, which contribute to their ability to drive a specific T cell response. For instance, LCs produce IL-15, which supports their ability to prime CTL responses (4,5). IL-15 was also shown to be important for Th17 induction by LCs (6,7).…”

“…In human skin, four different DC subsets have been described: Langerhans cells (LCs) that reside in the epidermis and three dermal DC populations that express either CD1a at an intermediate level (CD1a dim ) or CD14. The CD1a dim population is heterogeneous and contains CD141-expressing DCs (4). Each one of these subsets produces unique cytokines, which contribute to their ability to drive a specific T cell response.…”

“…Specific DC subtypes are specialized at inducing specific T cell responses. To achieve this, they use a unique set of costimulatory molecules and secrete specific cytokines (4). In human skin, four different DC subsets have been described: Langerhans cells (LCs) that reside in the epidermis and three dermal DC populations that express either CD1a at an intermediate level (CD1a dim ) or CD14.…”