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Wnt-3a Induces Cytokine Release in Human Mast Cells

Division of Immunology and Allergy, Department of Medicine Solna, Karolinska Institutet, and Karolinska University Hospital, 171 64 Stockholm, Sweden
Experimental Asthma and Allergy Research, Institute of Environmental Medicine (IMM), Karolinska Institutet, 171 77 Stockholm, Sweden
Section for Receptor Biology and Signaling, Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden
Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden
Authors to whom correspondence should be addressed.
Authors contributed equally.
On behalf of ChAMP collaborators Ann-Charlotte Orre, Mamdoh Al-Ameri, Mikael Adner and Sven-Erik Dahlén.
Cells 2019, 8(11), 1372;
Received: 14 October 2019 / Accepted: 29 October 2019 / Published: 1 November 2019
(This article belongs to the Section Cellular Immunology)
Mast cells are well known for their detrimental effects in allergies and asthma, and Wnt signaling has recently been implicated in asthma and other airway diseases. However, it is not known if or how Wnts affect human mast cells. Since Wnt expression is elevated in individuals with asthma and is linked to a Th2 profile, we hypothesized that mast cells could be affected by Wnts in the context of asthma. We therefore sought to investigate the role of Wnt signaling in human mast cell development and activation. We first examined the expression of the 10 main Wnt receptors, Frizzled 1–10 (FZD1–10), and found expression of several FZDs in human mast cells. Treatment with purified recombinant Wnt-3a or Wnt-5a did not affect the proliferation or maturation of CD34+ progenitors into mast cells, as indicated by cellular expression of CD117 and FcεRI, activation by FcεRI crosslinking, and histamine and tryptase release. Furthermore, Wnt treatment did not change the phenotype from MCT to MCTC, since MrgX2 expression, compound 48/80-mediated activation, and carboxypeptidase A3 content were not affected. However, Wnt-3a activated WNT/β-catenin signaling in mature human mast cells, as revealed by stabilization of β-catenin, upregulation of IL-8 and CCL8 mRNA expression, and release of IL-8 protein. Thus, our data suggest that Wnt-3a activation of mast cells could contribute to the recruitment of immune cells in conditions associated with increased Wnt-3a expression, such as asthma. View Full-Text
Keywords: mast cells; Wnt signaling; Wnt-3a; Frizzled; IL-8; CCL8; asthma mast cells; Wnt signaling; Wnt-3a; Frizzled; IL-8; CCL8; asthma
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MDPI and ACS Style

Tebroke, J.; Lieverse, J.E.; Säfholm, J.; Schulte, G.; Nilsson, G.; Rönnberg, E. Wnt-3a Induces Cytokine Release in Human Mast Cells. Cells 2019, 8, 1372.

AMA Style

Tebroke J, Lieverse JE, Säfholm J, Schulte G, Nilsson G, Rönnberg E. Wnt-3a Induces Cytokine Release in Human Mast Cells. Cells. 2019; 8(11):1372.

Chicago/Turabian Style

Tebroke, Julia, Joris E. Lieverse, Jesper Säfholm, Gunnar Schulte, Gunnar Nilsson, and Elin Rönnberg. 2019. "Wnt-3a Induces Cytokine Release in Human Mast Cells" Cells 8, no. 11: 1372.

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