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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3804399
- author
- Bergenfelz, Caroline
LU
; Janols, Helena
LU
; Wullt, Marlene
LU
; Jirström, Karin
LU
; Bredberg, Anders
LU
and Leandersson, Karin
LU
- organization
- publishing date
- 2013
- 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
- pmid:23679576
- ISSN
- 1365-3083
- DOI
- 10.1111/sji.12075
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Molecular Medicine (013031200), Infectious Diseases Research Unit (013242010), Pathology, (Lund) (013030000), Clinical Microbiology, Malmö (013011000)
- 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
- 2016-04-01 10:21:54
- date last changed
- 2024-01-29 02:53:54
@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}},
doi = {{10.1111/sji.12075}},
volume = {{78}},
year = {{2013}},
}