Transcriptional profiling reveals functional dichotomy between human slan+ non-classical monocytes and myeloid dendritic cells
(2017) In Journal of Leukocyte Biology 102(4). p.1055-1068- 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)
- 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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3bb3d77c-018b-4a4f-8822-2da1212eaf9f
- author
- 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.
- organization
- publishing date
- 2017-10
- 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
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:28720687
- 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
- 2022-03-24 21:33:03
@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}},
keywords = {{Dendritic cell subsets; Monocytes; Slan}},
language = {{eng}},
number = {{4}},
pages = {{1055--1068}},
publisher = {{John Wiley & Sons Inc.}},
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}},
doi = {{10.1189/jlb.3MA0117-037R}},
volume = {{102}},
year = {{2017}},
}