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

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van Leeuwen-Kerkhoff, NathalieVrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam (author)

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

Article/chapterEnglish2017

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2017

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LIBRIS-ID:oai:lup.lub.lu.se:3bb3d77c-018b-4a4f-8822-2da1212eaf9f
https://lup.lub.lu.se/record/3bb3d77c-018b-4a4f-8822-2da1212eaf9fURI
https://doi.org/10.1189/jlb.3MA0117-037RDOI

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Language:English
Summary in:English &Swedish

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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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Cell- och molekylärbiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Cell and Molecular Biology hsv//eng
Dendritic cell subsets
Monocytes
Slan

Added entries (persons, corporate bodies, meetings, titles ...)

Lundberg, KristinaLund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)medk-klu (author)
Westers, Theresia M.Amsterdam UMC - Vrije Universiteit Amsterdam,Vrije Universiteit Amsterdam (author)
Kordasti, ShahramKing's College Hospital,King's College London (author)
Bontkes, Hetty JAcademic Centre for Dentistry Amsterdam (author)
Gruijl, Tanja DVrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam (author)
Lindstedt, MalinLund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)immt-mli (author)
van de Loosdrecht, Arjan A.Amsterdam UMC - Vrije Universiteit Amsterdam,Vrije Universiteit Amsterdam (author)
Vrije Universiteit AmsterdamAmsterdam UMC - Vrije Universiteit Amsterdam (creator_code:org_t)

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In:Journal of Leukocyte Biology102:4, s. 1055-10680741-5400

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