RESUMEN
Dendritic cells (DCs), monocytes, and macrophages are leukocytes with critical roles in immunity and tolerance. The DC network is evolutionarily conserved; the homologs of human tissue CD141(hi)XCR1⺠CLEC9A⺠DCs and CD1c⺠DCs are murine CD103⺠DCs and CD64⻠CD11b⺠DCs. In addition, human tissues also contain CD14⺠cells, currently designated as DCs, with an as-yet unknown murine counterpart. Here we have demonstrated that human dermal CD14⺠cells are a tissue-resident population of monocyte-derived macrophages with a short half-life of <6 days. The decline and reconstitution kinetics of human blood CD14⺠monocytes and dermal CD14⺠cells in vivo supported their precursor-progeny relationship. The murine homologs of human dermal CD14⺠cells are CD11b⺠CD64⺠monocyte-derived macrophages. Human and mouse monocytes and macrophages were defined by highly conserved gene transcripts, which were distinct from DCs. The demonstration of monocyte-derived macrophages in the steady state in human tissue supports a conserved organization of human and mouse mononuclear phagocyte system.
Asunto(s)
Receptores de Lipopolisacáridos/metabolismo , Macrófagos/inmunología , Piel/inmunología , Animales , Antígeno CD11b/biosíntesis , Diferenciación Celular/inmunología , Linaje de la Célula/inmunología , Movimiento Celular/inmunología , Células Cultivadas , Células Dendríticas/inmunología , Femenino , Humanos , Memoria Inmunológica/inmunología , Ratones , Ratones Transgénicos , Receptores de IgG/biosíntesis , Piel/citología , Linfocitos T/inmunologíaRESUMEN
Dendritic cells (DCs), macrophages (Mφ), and T cells are major components of the skin immune system, but their interstitial spatial organization is poorly characterized. Using four-channel whole-mount immunofluorescence staining of the human dermis, we demonstrated the three-dimensional distribution of CD31(+) blood capillaries, LYVE-1(+) lymphatics, discrete populations of CD11c(+) myeloid DCs, FXIIIa(+) Mφ, and lymphocytes. We showed phenotypic and morphological differences in situ between DCs and Mφ. DCs formed the first dermal cellular layer (0-20 µm beneath the dermoepidermal junction), Mφ were located deeper (40-60 µm), and CD3(+) lymphocytes were observed throughout (0-60 µm). Below this level, DCs, T cells, and the majority of Mφ formed stable perivascular sheaths. Whole-mount imaging revealed the true extent of dermal leukocytes previously underestimated from cross-section views. The total area of apical dermis (0-30 µm) contained approximately 10-fold more myeloid DCs than the entire blood volume of an average individual. Surprisingly, <1% of dermal DCs occupied lymphatics in freshly isolated skin. Dermal DCs rapidly accumulated within lymphatics, but Mφ remained fixed in skin explants cultured ex vivo. The leukocyte architecture observed in normal skin was distorted in inflammation and disease. These studies illustrate the micro-anatomy of dermal leukocytes and provide further insights into their functional organization.