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

van Leeuwen-Kerkhoff, Nathalie; Lundberg, Kristina LU ; Westers, Theresia M.; Kordasti, Shahram ; Bontkes, Hetty J; Gruijl, Tanja D; Lindstedt, Malin LU and van de Loosdrecht, Arjan A. (2017) In Journal of Leukocyte Biology 102(4). p.1055-1068
Abstract (Swedish)
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... (More)
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. (Less)
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Dendritic cell subsets, Monocytes, Slan
in
Journal of Leukocyte Biology
volume
102
issue
4
pages
1055 - 1068
publisher
Society for Leukocyte Biology
external identifiers
  • scopus:85030671864
  • wos:000413396400010
ISSN
0741-5400
DOI
10.1189/jlb.3MA0117-037R
language
English
LU publication?
yes
id
3bb3d77c-018b-4a4f-8822-2da1212eaf9f
date added to LUP
2017-10-10 12:55:35
date last changed
2018-01-16 13:22:34
@article{3bb3d77c-018b-4a4f-8822-2da1212eaf9f,
  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. },
  author       = {van Leeuwen-Kerkhoff, Nathalie and Lundberg, Kristina and Westers, Theresia M. and Kordasti, Shahram  and Bontkes, Hetty J and Gruijl, Tanja D and Lindstedt, Malin and van de Loosdrecht, Arjan A.},
  issn         = {0741-5400},
  keyword      = {Dendritic cell subsets,Monocytes,Slan},
  language     = {eng},
  number       = {4},
  pages        = {1055--1068},
  publisher    = {Society for Leukocyte Biology},
  series       = {Journal of Leukocyte Biology},
  title        = {Transcriptional profiling reveals functional dichotomy between human slan+ non-classical monocytes and myeloid dendritic cells},
  url          = {http://dx.doi.org/10.1189/jlb.3MA0117-037R},
  volume       = {102},
  year         = {2017},
}