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Wnt5a induces a tolerogenic phenotype of macrophages in sepsis and breast cancer patients.
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- Bergenfelz, Caroline (author)
- Lund University,Lunds universitet,Institutionen för translationell medicin,Medicinska fakulteten,Department of Translational Medicine,Faculty of Medicine
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- Hagerling, Catharina (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Institutionen för translationell medicin,Experimentell patologi, Malmö,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Department of Translational Medicine,Experimental Pathology, Malmö,Lund University Research Groups
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- Ekström, Elin (author)
- Lund University,Lunds universitet,Experimentell patologi, Malmö,Forskargrupper vid Lunds universitet,Experimental Pathology, Malmö,Lund University Research Groups
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- (creator_code:org_t)
- 2012-06-01
- 2012
- English.
- In: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 188:11, s. 5448-5458
- Journal article (peer-reviewed)
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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- ref (subject category)
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