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Wnt5a inhibits human monocyte derived myeloid dendritic cell generation.

Bergenfelz, Caroline LU ; Janols, Helena LU ; Wullt, Marlene LU ; Jirström, Karin LU ; Bredberg, Anders LU and Leandersson, Karin LU (2013) In Scandinavian Journal of Immunology 78(2). p.194-204
Abstract
Wnt5a is a non-canonical Wnt protein that is expressed at elevated levels in inflammatory conditions. Its role in inflammation remains unclear, although it is known that Wnt5a is expressed at a higher level in monocyte-derived myeloid dendritic cells (Mo-mDCs) than in monocytes and macrophages. The function of Wnt5a in dendritic cells (DCs) remains relatively unexplored. Here, we found that under Mo-mDC culture conditions, Wnt5a inhibited the generation of CD14(+/low) Mo-mDCs while promoting the generation of CD14(+/++) CD16(+) monocytes. We could further show that stimulation of monocytes with rWnt5a induced a rapid IL-6 production and that the rWnt5a treated Mo-mDC differentiation was restored upon blocking of IL-6. Also conditioned... (More)
Wnt5a is a non-canonical Wnt protein that is expressed at elevated levels in inflammatory conditions. Its role in inflammation remains unclear, although it is known that Wnt5a is expressed at a higher level in monocyte-derived myeloid dendritic cells (Mo-mDCs) than in monocytes and macrophages. The function of Wnt5a in dendritic cells (DCs) remains relatively unexplored. Here, we found that under Mo-mDC culture conditions, Wnt5a inhibited the generation of CD14(+/low) Mo-mDCs while promoting the generation of CD14(+/++) CD16(+) monocytes. We could further show that stimulation of monocytes with rWnt5a induced a rapid IL-6 production and that the rWnt5a treated Mo-mDC differentiation was restored upon blocking of IL-6. Also conditioned media from Wnt5a stimulated human breast cancer cells producing IL-6, specifically inhibited Mo-mDC differentiation. These observations are strengthened by our finding that patients with sepsis, a disease involving elevated Wnt5a and IL-6 levels, also showed a significant increase in the CD14(+) CD16(++) /CD14(+/++) CD16(+) monocyte populations, which was accompanied by a significant decrease in circulating mDCs. We finally show that under typical Mo-mDC culture conditions, monocytes isolated from sepsis patients as compared to healthy controls, preferentially differentiated into CD14(+/++) HLA-DR(++) cells. We suggest that Wnt5a is a possible candidate mediator for the CD14(+/++) CD16(+) monocyte accumulation seen in infectious disease and cancer patients. This article is protected by copyright. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scandinavian Journal of Immunology
volume
78
issue
2
pages
194 - 204
publisher
Wiley-Blackwell
external identifiers
  • wos:000322014700011
  • pmid:23679576
  • scopus:84880689920
ISSN
1365-3083
DOI
10.1111/sji.12075
language
English
LU publication?
yes
id
f4290dd7-d2ec-4262-ba1e-6d7a173dfa50 (old id 3804399)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23679576?dopt=Abstract
date added to LUP
2013-06-06 20:05:40
date last changed
2019-04-07 03:10:17
@article{f4290dd7-d2ec-4262-ba1e-6d7a173dfa50,
  abstract     = {Wnt5a is a non-canonical Wnt protein that is expressed at elevated levels in inflammatory conditions. Its role in inflammation remains unclear, although it is known that Wnt5a is expressed at a higher level in monocyte-derived myeloid dendritic cells (Mo-mDCs) than in monocytes and macrophages. The function of Wnt5a in dendritic cells (DCs) remains relatively unexplored. Here, we found that under Mo-mDC culture conditions, Wnt5a inhibited the generation of CD14(+/low) Mo-mDCs while promoting the generation of CD14(+/++) CD16(+) monocytes. We could further show that stimulation of monocytes with rWnt5a induced a rapid IL-6 production and that the rWnt5a treated Mo-mDC differentiation was restored upon blocking of IL-6. Also conditioned media from Wnt5a stimulated human breast cancer cells producing IL-6, specifically inhibited Mo-mDC differentiation. These observations are strengthened by our finding that patients with sepsis, a disease involving elevated Wnt5a and IL-6 levels, also showed a significant increase in the CD14(+) CD16(++) /CD14(+/++) CD16(+) monocyte populations, which was accompanied by a significant decrease in circulating mDCs. We finally show that under typical Mo-mDC culture conditions, monocytes isolated from sepsis patients as compared to healthy controls, preferentially differentiated into CD14(+/++) HLA-DR(++) cells. We suggest that Wnt5a is a possible candidate mediator for the CD14(+/++) CD16(+) monocyte accumulation seen in infectious disease and cancer patients. This article is protected by copyright. All rights reserved.},
  author       = {Bergenfelz, Caroline and Janols, Helena and Wullt, Marlene and Jirström, Karin and Bredberg, Anders and Leandersson, Karin},
  issn         = {1365-3083},
  language     = {eng},
  number       = {2},
  pages        = {194--204},
  publisher    = {Wiley-Blackwell},
  series       = {Scandinavian Journal of Immunology},
  title        = {Wnt5a inhibits human monocyte derived myeloid dendritic cell generation.},
  url          = {http://dx.doi.org/10.1111/sji.12075},
  volume       = {78},
  year         = {2013},
}