TY - JOUR
T1 - Transcriptional profiling reveals functional dichotomy between human slan+ non-classical monocytes and myeloid dendritic cells
AU - van Leeuwen-Kerkhoff, Nathalie
AU - Lundberg, Kristina
AU - Westers, Theresia M.
AU - Kordasti, Shahram
AU - Bontkes, Hetty J.
AU - de Gruijl, Tanja D.
AU - Lindstedt, Malin
AU - van de Loosdrecht, Arjan A.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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 geneexpression 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-1b 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.
AB - 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 geneexpression 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-1b 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.
KW - CD141 DC
KW - CD1c DC
KW - M-DC8 cells
KW - Microarray
UR - http://www.scopus.com/inward/record.url?scp=85030671864&partnerID=8YFLogxK
U2 - https://doi.org/10.1189/jlb.3MA0117-037R
DO - https://doi.org/10.1189/jlb.3MA0117-037R
M3 - Article
C2 - 28720687
SN - 0741-5400
VL - 102
SP - 1055
EP - 1068
JO - Journal of leukocyte biology
JF - Journal of leukocyte biology
IS - 4
ER -