FcγRIII (CD16) equips immature 6-sulfo LacNAc–expressing dendritic cells (slanDCs) with a unique capacity to handle IgG-complexed antigens

Abstract

Key Points• The expression of CD16 by immature slanDCs equips these cells with a unique capacity to handle immune complexes.• CD16 expression on slanDCs is rapidly downregulated during maturation by activation of ADAM10 and ADAM17. We show that CD16 is rapidly shed from the surface of maturing slanDCs, resulting from the combined action of the metalloproteinases ADAM10 and ADAM17. In conclusion, these data provide strong evidence that slanDCs play an important role in IC-driven immune responses. (Blood. 2013;121(18):3609-3618)

Mononuclear phagocytes and marker modulation: when CD16 disappears, CD38 takes the stage

“…In conjunction with the results presented by Döbel et al, 1 our data thus demonstrate that the process of ectodomain shedding of 2 distinct surface receptors occurs in the same circumstances and by overlapping mechanisms in both nonclassical monocytes (and slanDCs) and classical monocytes, underscoring the similarities between the activation-dependent enzymatic machinery of 2 closely related monocyte family members. Furthermore, we show that TLR engagement can drive a response that overcomes the inhibition exerted by red blood cells in nonclassical monocytes.…”

“…We have read with great interest the article from Döbel et al, 1 which shows the ability of freshly separated 6-sulfo LacNac (slan)-positive dendritic cells (slanDCs) to internalize immunoglobulin G (IgG)-opsonized particles and aggregated IgG via FcgRIIIA/CD16-dependent phagocytosis. SlanDCs are a subset of "nonclassical monocytes" expressing CD16.…”

“…1 We noted the downregulation of CD16 in all CD16-expressing mononuclear myeloid cells in experiments analyzing the cytokine response to Toll-like receptor (TLR) 4 and TLR7/8 agonists in lithium-heparinized whole blood (and thus in the presence of erythrocytes) (Figure 1A-C). As shown in Figure 1C, this modulation is concomitant with the production of tumor necrosis factor a (TNFa).…”

Plasmodium falciparum Infection of Human Volunteers Activates Monocytes and CD16 + Dendritic Cells and Induces Upregulation of CD16 and CD1c Expression

“…Further studies are needed to resolve these discrepancies, which might also relate to the degree of parasitemia. Moreover, future studies should investigate whether these CD16 mDCs might be constituted of so-called 6-sulfo LacNAc ϩ dendritic cells (slanDCs), an inflammatory DC type with unique capacities in immune complex-associated antigen capture, T-cell priming, and antibody-dependent cellular cytotoxicity (20,24,25). These cells are specifically recruited to sites of inflammation (25), which might explain field findings of reduced circulating CD16 mDC frequencies during more-prolonged infection in areas of endemicity (16).…”

“…In addition to HLA-peptide recognition, protection against malaria is associated with ␥␦T cells expressing invariant T-cell receptors, which can be activated by lipid-presenting molecules of the CD1 family (18,19). Antigen uptake for presentation is further mediated not only by endocytosis, as examined previously (8,16), but also, for instance, by phagocytosis of immune complex-associated antigens, which can be facilitated by the Fc␥III receptor CD16 (20).…”