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Hofer, Thomas P.; Zawada, Adam M.; Frankenberger, Marion; Skokann, Kerstin; Satzl, Anna A.; Gesierich, Wolfgang; Schuberth, Madeleine; Levin, Johannes; Danek, Adrian; Rotter, Björn; Heine, Gunnar H.; Ziegler-Heitbrock, Loems
Blood, 12/2015, Letnik: 126, Številka: 24Journal Article
Human monocytes are subdivided into classical, intermediate, and nonclassical subsets, but there is no unequivocal strategy to dissect the latter 2 cell types. We show herein that the cell surface marker 6-sulfo LacNAc (slan) can define slan-positive CD14+CD16++ nonclassical monocytes and slan-negative CD14++CD16+ intermediate monocytes. Gene expression profiling confirms that slan-negative intermediate monocytes show highest expression levels of major histocompatibility complex class II genes, whereas a differential ubiquitin signature is a novel feature of the slan approach. In unsupervised hierarchical clustering, the slan-positive nonclassical monocytes cluster with monocytes and are clearly distinct from CD1c+ dendritic cells. In clinical studies, we show a selective increase of the slan-negative intermediate monocytes to >100 cells per microliter in patients with sarcoidosis and a fivefold depletion of the slan-positive monocytes in patients with hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS), which is caused by macrophage colony-stimulating factor (M-CSF) receptor mutations. These data demonstrate that the slan-based definition of CD16-positive monocyte subsets is informative in molecular studies and in clinical settings. •The slan marker can be used to define nonclassical and intermediate monocytes in human blood.•slan-negative intermediate monocytes are expanded in sarcoidosis, and slan-positive nonclassical monocytes are depleted in HDLS.
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