Wnt5a induces a tolerogenic phenotype of macrophages in sepsis and breast cancer patients.
Author
Summary, in English
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.
Department/s
- Department of Translational Medicine
- Experimental Pathology, Malmö
- Tumor microenvironment
- Infectious Diseases Research Unit
- Clinical Microbiology, Malmö
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2012
Language
English
Pages
5448-5458
Publication/Series
Journal of immunology
Volume
188
Issue
11
Links
Document type
Journal article
Publisher
American Association of Immunologists
Topic
- Immunology in the medical area
Status
Published
Research group
- Experimental Pathology, Malmö
- Infectious Diseases Research Unit
- Clinical Microbiology, Malmö
ISBN/ISSN/Other
- ISSN: 1550-6606