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 (författare)

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

Artikel/kapitelEngelska2017

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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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Språk:engelska
Sammanfattning på:engelska &svenska

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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.

Ämnesord och genrebeteckningar

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

Biuppslag (personer, institutioner, konferenser, titlar ...)

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 (författare)
Westers, Theresia M.Amsterdam UMC - Vrije Universiteit Amsterdam,Vrije Universiteit Amsterdam (författare)
Kordasti, ShahramKing's College Hospital,King's College London (författare)
Bontkes, Hetty JAcademic Centre for Dentistry Amsterdam (författare)
Gruijl, Tanja DVrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam (författare)
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 (författare)
van de Loosdrecht, Arjan A.Amsterdam UMC - Vrije Universiteit Amsterdam,Vrije Universiteit Amsterdam (författare)
Vrije Universiteit AmsterdamAmsterdam UMC - Vrije Universiteit Amsterdam (creator_code:org_t)

Sammanhörande titlar

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

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