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slan-defined subsets of CD16-positive monocytes: impact of granulomatous inflammation and M-CSF receptor mutation.

Abstract
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.
AuthorsThomas P Hofer, Adam M Zawada, Marion Frankenberger, Kerstin Skokann, Anna A Satzl, Wolfgang Gesierich, Madeleine Schuberth, Johannes Levin, Adrian Danek, Björn Rotter, Gunnar H Heine, Loems Ziegler-Heitbrock
JournalBlood (Blood) Vol. 126 Issue 24 Pg. 2601-10 (Dec 10 2015) ISSN: 1528-0020 [Electronic] United States
PMID26443621 (Publication Type: Journal Article)
Copyright© 2015 by The American Society of Hematology.

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