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Wnt5a induces a tolerogenic phenotype of macrophages in sepsis and breast cancer patients.

Bergenfelz, Caroline LU ; Hagerling, Catharina LU ; Ekström, Elin LU ; Jirström, Karin LU ; Janols, Helena LU ; Wullt, Marlene LU ; Bredberg, Anders LU and Leandersson, Karin LU (2012) In Journal of immunology (Baltimore, Md. : 1950) 188(11). p.5448-5458
Abstract
A well-orchestrated inflammatory reaction involves the induction of effector functions and, at a later stage, an active downregulation of this potentially harmful process. In this study we show that under proinflammatory conditions the noncanonical Wnt protein, Wnt5a, induces immunosuppressive macrophages. The suppressive phenotype induced by Wnt5a is associated with induction of IL-10 and inhibition of the classical TLR4-NF-κB signaling. Interestingly, this phenotype closely resembles that observed in reprogrammed monocytes in sepsis patients. The Wnt5a-induced feedback inhibition is active both during in vitro LPS stimulation of macrophages and in patients with sepsis caused by LPS-containing, Gram-negative bacteria. Furthermore, using... (More)
A well-orchestrated inflammatory reaction involves the induction of effector functions and, at a later stage, an active downregulation of this potentially harmful process. In this study we show that under proinflammatory conditions the noncanonical Wnt protein, Wnt5a, induces immunosuppressive macrophages. The suppressive phenotype induced by Wnt5a is associated with induction of IL-10 and inhibition of the classical TLR4-NF-κB signaling. Interestingly, this phenotype closely resembles that observed in reprogrammed monocytes in sepsis patients. The Wnt5a-induced feedback inhibition is active both during in vitro LPS stimulation of macrophages and in patients with sepsis caused by LPS-containing, Gram-negative bacteria. Furthermore, using breast cancer patient tissue microarrays, we find a strong correlation between the expression of Wnt5a in malignant epithelial cells and the frequency of CD163(+) anti-inflammatory tumor-associated macrophages. In conclusion, our data point out Wnt5a as a potential target for an efficient therapeutic modality in severe human diseases as diverse as sepsis and malignancy. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of immunology (Baltimore, Md. : 1950)
volume
188
issue
11
pages
5448 - 5458
publisher
American Association of Immunologists
external identifiers
  • WOS:000304282200031
  • PMID:22547701
  • Scopus:84862066130
ISSN
1550-6606
DOI
10.4049/jimmunol.1103378
language
English
LU publication?
yes
id
b4ac04e5-6556-455f-b06a-0ab0000d5041 (old id 2609265)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22547701?dopt=Abstract
date added to LUP
2012-06-01 13:08:50
date last changed
2016-11-13 04:26:54
@misc{b4ac04e5-6556-455f-b06a-0ab0000d5041,
  abstract     = {A well-orchestrated inflammatory reaction involves the induction of effector functions and, at a later stage, an active downregulation of this potentially harmful process. In this study we show that under proinflammatory conditions the noncanonical Wnt protein, Wnt5a, induces immunosuppressive macrophages. The suppressive phenotype induced by Wnt5a is associated with induction of IL-10 and inhibition of the classical TLR4-NF-κB signaling. Interestingly, this phenotype closely resembles that observed in reprogrammed monocytes in sepsis patients. The Wnt5a-induced feedback inhibition is active both during in vitro LPS stimulation of macrophages and in patients with sepsis caused by LPS-containing, Gram-negative bacteria. Furthermore, using breast cancer patient tissue microarrays, we find a strong correlation between the expression of Wnt5a in malignant epithelial cells and the frequency of CD163(+) anti-inflammatory tumor-associated macrophages. In conclusion, our data point out Wnt5a as a potential target for an efficient therapeutic modality in severe human diseases as diverse as sepsis and malignancy.},
  author       = {Bergenfelz, Caroline and Hagerling, Catharina and Ekström, Elin and Jirström, Karin and Janols, Helena and Wullt, Marlene and Bredberg, Anders and Leandersson, Karin},
  issn         = {1550-6606},
  language     = {eng},
  number       = {11},
  pages        = {5448--5458},
  publisher    = {ARRAY(0xa4c2cf0)},
  series       = {Journal of immunology (Baltimore, Md. : 1950)},
  title        = {Wnt5a induces a tolerogenic phenotype of macrophages in sepsis and breast cancer patients.},
  url          = {http://dx.doi.org/10.4049/jimmunol.1103378},
  volume       = {188},
  year         = {2012},
}