Wnt5a inhibits human monocyte derived myeloid dendritic cell generation.

Summary, in English

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: Caroline Bergenfelz; Helena Janols; Marlene Wullt; Karin Jirström; Anders Bredberg; Karin Leandersson
• Department/s: Department of Translational Medicine; Infectious Diseases Research Unit; Tumor microenvironment; Clinical Microbiology, Malmö; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publishing year: 2013
• Language: English
• Pages: 194-204
• Publication/Series: Scandinavian Journal of Immunology
• Volume: 78
• Issue: 2
• Links: http://www.ncbi.nlm.nih.gov/pubmed/23679576?dopt=Abstract; http://dx.doi.org/10.1111/sji.12075
• Document type: Journal article
• Publisher: Wiley-Blackwell
• Topic: Immunology in the medical area
• Status: Published
• Research group: Infectious Diseases Research Unit; Clinical Microbiology, Malmö
• ISBN/ISSN/Other: ISSN: 1365-3083