Transcriptional profiling reveals functional dichotomy between human slan+ non-classical monocytes and myeloid dendritic cells

Abstract

Human 6-sulfo LacNac-positive (slan) cells have been subject to a paradigm debate. They have previously been classified as a distinct dendritic cell (DC) subset. However, evidence has emerged that they may be more related to monocytes than to DCs. To gain deeper insight into the functional specialization of slan cells, we have compared them with both conventional myeloid DC subsets (CD1c and CD141) in human peripheral blood (PB). With the use of genome-wide transcriptional profiling, as well as functional tests, we clearly show that slan cells form a distinct, non-DC-like population. They cluster away from both DC subsets, and their gene-expression profile evidently suggests involvement in distinct inflammatory processes. An extensive transcriptional meta-analysis confirmed the relationship of slan cells with the monocytic compartment rather than with DCs. From a functional perspective, their ability to prime CD4 and CD8 T cells is relatively low. Combined with the finding that "antigen presentation by MHC class II" is at the top of under-represented pathways in slan cells, this points to a minimal role in directing adaptive T cell immunity. Rather, the higher expression levels of complement receptors on their cell surface, together with their high secretion of IL-1β and IL-6, imply a specific role in innate inflammatory processes, which is consistent with their recent identification as non-classical monocytes. This study extends our knowledge on DC/monocyte subset biology under steady-state conditions and contributes to our understanding of their role in immune-mediated diseases and their potential use in immunotherapeutic strategies.

Human dendritic cell subsets: an update

“…Concerning the question of whether SLAN + cells are monocytes or DC, their gene expression is clearly monocytic. 13,[198][199][200] Furthermore, recent human in vivo and xenograft experiments support the hypothesis that non-classical monocytes differentiate from classical monocytes by down-regulating inflammatory pathways and adopting a CX3CR + CCR2 -CD11c hi CD11b lo phenotype. 201 However, it should be noted that gene expression alone does not absolutely exclude an independent origin of SLAN + cells from the remainder of CD16 + monocytes and that SLAN itself was not measured on the output of cells derived from human classical monocytes in the adoptive transfer experiments.…”

“…The simple facts are that CD16 + monocytes are heterogeneous and that SLAN expression identifies a subpopulation with lower CD11b, CD14 and CD36 but higher expression of CD16. Concerning the question of whether SLAN + cells are monocytes or DC, their gene expression is clearly monocytic . Furthermore, recent human in vivo and xenograft experiments support the hypothesis that non‐classical monocytes differentiate from classical monocytes by down‐regulating inflammatory pathways and adopting a CX3CR + CCR2 – CD11c hi CD11b lo phenotype .…”

Intracapillary immune complexes recruit and activate slan-expressing CD16+ monocytes in human lupus nephritis

“…DCs, monocytes, and macrophages are now classified based on their identified precursor cell. For slan + cells, transcriptomic studies collectively demonstrated a gene signature shared with monocytes rather than bona fide DCs (18). We therefore propose calling these cells slanMo instead of slanDCs, as already recommended by others (19).…”

Clinical Implication of Multi-Parameter Flow Cytometry in Myelodysplastic Syndromes

“…Several other hematopoietic cell subsets, involved in the dysplastic clone and/or in the immunopathogenesis of MDS, have been described, including aberrancies in mast cells, changes of frequency in plasmacytoid dendritic cells, myeloid dendritic cells (mDC1 and mDC2), myeloid-derived suppressor cells (MDSC) and T cell subsets [24,25]. Increased frequencies of MDSCs and T-regulatory cells are thought to reflect an immunosuppressive environment in high risk MDS [2,26].…”