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

Slan+ non‐classical monocytes are equipped with a distinctive immunological gene set compared to DCs, and harbor monocyte‐like functional features. Human 6‐sulfo LacNac‐positive (slan+) cells have been subject to a paradigm debate. They have previously been classified as a distinct dendritic cell (D...

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Bibliographic Details
Published in:Journal of leukocyte biology Vol. 102; no. 4; pp. 1055 - 1068
Main Authors: Leeuwen‐Kerkhoff, Nathalie, Lundberg, Kristina, Westers, Theresia M., Kordasti, Shahram, Bontkes, Hetty J., Gruijl, Tanja D., Lindstedt, Malin, Loosdrecht, Arjan A.
Format: Journal Article
Language:English
Published: Bethesda, MD, USA Society for Leukocyte Biology 01.10.2017
Oxford University Press
Subjects:
Antigen presentation
Antigens, CD1 - immunology
Antigens, Surface - immunology
Basic Medicine
CD141+ DC
CD1c antigen
CD1c+ DC
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cell and Molecular Biology
Cell surface
Cell- och molekylärbiologi
Complement receptors
Dendritic cells
Dendritic Cells - cytology
Dendritic Cells - immunology
Gene expression
Gene Expression Profiling
Genomes
Glycoproteins - immunology
Humans
Immunity
Immunology
Inflammation
Interleukin 6
Interleukin-1beta - immunology
Interleukin-6 - immunology
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Medical and Health Sciences
Medicin och hälsovetenskap
Medicinska och farmaceutiska grundvetenskaper
microarray
Monocytes
Monocytes - cytology
Monocytes - immunology
M‐DC8+ cells
Peripheral blood
Receptors
Specialization
Transcription
Transcription, Genetic - immunology
Tumor Suppressor Proteins
microarray
M-DC8+ cells
CD1c+ DC
CD141+ DC
ISSN:0741-5400, 1938-3673, 1938-3673
Online Access:Get full text
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Summary:Slan+ non‐classical monocytes are equipped with a distinctive immunological gene set compared to DCs, and harbor monocyte‐like functional features. 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.
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ISSN:0741-5400
1938-3673
1938-3673
DOI:10.1189/jlb.3MA0117-037R