Origins and Functional Specialization of Macrophages and of Conventional and Monocyte-Derived Dendritic Cells in Mouse Skin

Abstract

In the skin, the lack of markers permitting the unambiguous identification of macrophages and of conventional and monocyte-derived dendritic cells (DCs) complicates understanding of their contribution to skin integrity and to immune responses. By combining CD64 and CCR2 staining, we successfully identified each of these cell types and studied their origin, transcriptomic signatures, and migratory and T cell stimulatory properties. We also analyzed the impact of microbiota on their development and their contribution to skin inflammation during contact hypersensitivity. Dermal macrophages had a unique scavenging role and were unable to migrate and activate T cells. Conventional dermal DCs excelled both at migrating and activating T cells. In the steady-state dermis, monocyte-derived DCs are continuously generated by extravasated Ly-6C(hi) monocytes. Their T cell stimulatory capacity combined with their poor migratory ability made them particularly suited to activate skin-tropic T cells. Therefore, a high degree of functional specialization occurs among the mononuclear phagocytes of the skin.

Monocyte-Derived Dendritic Cells Promote Th Polarization, whereas Conventional Dendritic Cells Promote Th Proliferation

“…Two additional markers CD64 and MAR1 were used to further delineate moDCs from CD11b + cDCs (Fig. 1A) (20,36). We confirmed our previously reported findings that moDCs are rare in the steady state but become abundant in inflammation such as infection with Listeria (12,35) or where systemic levels of GM-CSF are high, such as in GM-CSF transgenic mice (35).…”

“…We observed that these Ly6C + CCR2 + moDCs also become abundant in mice immunized with CFA (17) and in mice with high levels of GM-CSF (35). Because Ly6C can be downregulated, additional markers like CD64 and MAR1 have been applied to distinguish moDCs in peripheral tissues (skin and lung) from lymph-resident cDCs (20,36). In this study, splenic moDCs also express CD64 and MAR1.…”

Functional Langerinhigh-Expressing Langerhans-like Cells Can Arise from CD14highCD16− Human Blood Monocytes in Serum-Free Condition

“…Indeed, it has been shown that LCs may originate from dermal CD14 + cells in noninflammatory settings in vitro (19). Other studies based on transcriptomic analyses have allowed reconsidering such CD14 + dermal cells as monocyte-derived macrophages most likely related to blood monocytes/macrophages rather than bona fide dermal DCs (20)(21)(22). However, whether these human monocyte-derived macrophages could differentiate into other cell types such as LCs in inflammatory conditions or at steady-state in vivo is still unclear.…”

Red Light Modulates Ultraviolet-Induced Gene Expression in the Epidermis of Hairless Mice

“…Recent studies showed that CD11b+ dermal dendritic cells have a phenotype that overlaps with that of dermal macrophages, and are substantially more abundant in steady state epidermis than in activated infiltrating cells. 27 It is tempting to speculate that an increase in expression of CD11 after LLLT was the result of de novo expression of the CD11b marker in the dendritic cells or other noninflammatory skin dwellers.…”