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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| Published in: | Journal of leukocyte biology Vol. 102; no. 4; pp. 1055 - 1068 |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Bethesda, MD, USA
Society for Leukocyte Biology
01.10.2017
Oxford University Press |
| Subjects: | |
| ISSN: | 0741-5400, 1938-3673, 1938-3673 |
| Online Access: | Get full text |
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| Abstract | 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. |
|---|---|
| AbstractList | 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. 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. 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. 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. 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.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. 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. 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 | Lindstedt, Malin Lundberg, Kristina Gruijl, Tanja D. Loosdrecht, Arjan A. Leeuwen‐Kerkhoff, Nathalie Bontkes, Hetty J. Westers, Theresia M. Kordasti, Shahram |
| Author_xml | – sequence: 1 givenname: Nathalie surname: Leeuwen‐Kerkhoff fullname: Leeuwen‐Kerkhoff, Nathalie – sequence: 2 givenname: Kristina surname: Lundberg fullname: Lundberg, Kristina – sequence: 3 givenname: Theresia M. surname: Westers fullname: Westers, Theresia M. – sequence: 4 givenname: Shahram surname: Kordasti fullname: Kordasti, Shahram – sequence: 5 givenname: Hetty J. surname: Bontkes fullname: Bontkes, Hetty J. – sequence: 6 givenname: Tanja D. surname: Gruijl fullname: Gruijl, Tanja D. – sequence: 7 givenname: Malin surname: Lindstedt fullname: Lindstedt, Malin – sequence: 8 givenname: Arjan A. surname: Loosdrecht fullname: Loosdrecht, Arjan A. email: a.vandeloosdrecht@vumc.nl |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28720687$$D View this record in MEDLINE/PubMed |
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| Snippet | Slan+ non‐classical monocytes are equipped with a distinctive immunological gene set compared to DCs, and harbor monocyte‐like functional features.
Human... 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)... 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)... Slan+ non-classical monocytes are equipped with a distinctive immunological gene set compared to DCs, and harbor monocyte-like functional features.Human... |
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| SubjectTerms | 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 |
| Title | Transcriptional profiling reveals functional dichotomy between human slan+ non‐classical monocytes and myeloid dendritic cells |
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