6-Sulfo LacNAc, a Novel Carbohydrate Modification of PSGL-1, Defines an Inflammatory Type of Human Dendritic Cells

Abstract

The monoclonal antibody M-DC8 defines a major subset of human blood dendritic cells (DCs). Here we identify the M-DC8 structure as 6-sulfo LacNAc, a novel carbohydrate modification of the P selectin glycoprotein ligand 1 (PSGL-1). In contrast to previously described blood DCs, M-DC8+ DCs lack the cutaneous lymphocyte antigen (CLA) on PSGL-1 and fail to bind P and E selectin. Yet they express anaphylatoxin receptors (C5aR and C3aR) and the Fcgamma receptor III (CD16), which recruit cells to inflammatory sites. While sharing with DC1 the expression of myeloid markers and a potent capacity to prime T cells in vitro, M-DC8+ DCs produce far more TNF-alpha in response to the bacterial endotoxin lipopolysaccharide (LPS). Thus, 6-sulfo LacNAc-expressing DCs appear as a novel proinflammatory DC subset.

FcγR expression on NK cells influences disease severity in rheumatoid arthritis

“…49 Interestingly, a CD16 þ DC subset with an increased capacity to secrete inflammatory cytokines has been identified. 50 Thus, it is possible that polymorphisms in the CD16 (FcgRIIIA) gene could affect DC function and phenotype.…”

slanDCs selectively accumulate in carcinoma-draining lymph nodes and marginate metastatic cells

“…Functionally, slanDCs stand out for their remarkable capacity to produce tumour necrosis factor alpha (TNFa) and IL-12p70 upon stimulation with discrete toll-like receptor ligands 13,14 . In addition, they are potent inducers of primary antigen-specific T-cell responses in vitro 11 , and show a superior programming of Th1/Th17 cell polarization as compared with classical CD1c þ DCs 14 . Furthermore, slanDCs induce in vitro tumour-specific cytotoxic T cells and strongly promote natural killer (NK) cell proliferation, NK cytotoxic activity and, in cooperation with neutrophils, NK-derived interferon-gamma (IFNg) production [15][16][17] .…”

Acute myeloid leukemia cells fail to activate native human dendritic cells: a potential mechanism of immune evasion

“…1,2 Hypoxia is associated to angiogenesis in solid tumors and hypoxia-inducible factor (HIF)-1a is a critical trigger and regulator of the angiogenic switch. 3,4 It is known that the BM microenvironment is hypoxic in healthy subjects, 5 however, the BM oxygen levels in patients with MM have never been investigated and the effects of hypoxia and its main transcription factor HIF-1a on the transcriptional and proangiogenic profiles of CD138 þ cells are not known.…”

“…In previous studies, we have shown that activated slanDCs produce large amounts of TNF-a, which essentially contributes to their tumor-directed cytotoxicity. 5,7 In addition, we have shown that activated slanDCs are principal producers of IL-12, which favors the differentiation of naive CD4 þ T cells into Th1 cells and is important in NK cell activation. 6,8 Blood samples were obtained from healthy donors with informed consent.…”

“…Recently, we defined 6-sulfo LacNAc (slan)DCs (formerly termed M-DC8 þ DCs) as a major subpopulation of proinflammatory myeloid human blood DCs, which mainly differ from other blood DC subsets by their selective phenotype (6- 5,6 Functional data revealed that slanDCs can mediate tumor-directed cytotoxicity and efficiently activate tumor-reactive NK cells and CD8 þ CTLs. 7 To get novel insights into the impact of primary human AML cells on native human DCs, we investigated the capacity of AML cells to modulate the secretion of TNF-a and IL-12 by slanDCs.…”