Normal human dermis contains distinct populations of CD11c+BDCA-1+ dendritic cells and CD163+FXIIIA+ macrophages

Abstract

We used a panel of monoclonal antibodies to characterize DCs in the dermis of normal human skin. Staining for the CD11c integrin, which is abundant on many kinds of DCs, revealed cells in the upper dermis. These cells were positive for blood DC antigen-1 (BDCA-1; also known as CD1c), HLA-DR, and CD45, markers that are also expressed by circulating myeloid DCs. A small subset of CD11c + dermal cells expressed DEC-205/ CD205 and DC-lysosomal-associated membrane glycoprotein/CD208 (DC-LAMP/CD208), suggesting some differentiation or maturation. When BDCA-1 + cells were selected from collagenase digests of normal dermis, they proved to be strong stimulators for T cells in a mixed leukocyte reaction. A second major population of cells located throughout the dermis was positive for factor XIIIA (FXIIIA), but lacked CD11c and BDCA-1. They expressed the macrophage scavenger receptor CD163 and stained weakly for HLA-DR and CD45. Isolated CD163 + dermal cells were inactive in stimulating T cell proliferation, but in biopsies of tattoos, these cells were selectively laden with granular pigments. Plasmacytoid DCs were also present in the dermis, marked by CD123 and BDCA-2. In summary, the normal dermis contains typical immunostimulatory myeloid DCs identified by CD11c and BDCA-1, as well as an additional population of poorly stimulatory macrophages marked by CD163 and FXIIIA.

Immunoglobulin-like transcript receptors on human dermal CD14+dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming

“…Several populations of DCs take up residence in different tissues and carry common as well as unique biological functions (2,3). The healthy human skin displays at least three DC populationsLangerhans cells (LCs) in the epidermis and interstitial CD1a + and CD14 + DCs in the dermis (4,5). Each of the different skin DC subsets carries out specialized functions.…”

Possible role for cellular FXIII in monocyte-derived dendritic cell motility

“…FXIII-A is also expressed in some subpopulations of dendritic cells (DCs) such as migratory dermal DCs (Nestle et al, 1993), DC-like cells derived from CD34+ progenitor cells (Caux et al, 1996), a subset of dermal cells termed ¨dermal dendrocytes¨ (Cerio et al, 1989;Quatresooz et al, 2008), and in vitro monocyte-derived DCs (Grassi et al, 1998). It has also been recently identified in a population of dermal cells with a marked plasticity between tissue-resident DCs and macrophages (Zaba et al, 2007), suggesting that FXIII-A expression may associate to an alternative cellular activation state following the stimulation of DCs and macrophages by IL-4 (Nestle and Nickoloff, 2007).…”

Auditing Protein Therapeutics Management by Professional APCs: Toward Prevention of Immune Responses against Therapeutic Proteins

“…Whether such macrophage populations exist in human and are capable of Ag-presenting function remains to be confirmed. In another recent study, normal human dermis has been shown to contain immunostimulatory dendritic cells marked by CD11c and BDCA-1 while the macrophage population identified by CD163 and factor XIIIA showed much less immunostimulatory potency (23).…”