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Wnt-3a Induces Cytokine Release in Human Mast Cells
Karolinska Inst, Dept Med Solna, Div Immunol & Allergy, S-17164 Stockholm, Sweden;Karolinska Univ Hosp, S-17164 Stockholm, Sweden.
Karolinska Inst, Dept Med Solna, Div Immunol & Allergy, S-17164 Stockholm, Sweden;Karolinska Univ Hosp, S-17164 Stockholm, Sweden.
Karolinska Inst, Inst Environm Med IMM, Expt Asthma & Allergy Res, S-17177 Stockholm, Sweden.
Karolinska Inst, Dept Physiol & Pharmacol, Sect Receptor Biol & Signaling, S-17177 Stockholm, Sweden.ORCID iD: 0000-0002-2700-7013
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2019 (English)In: CELLS, ISSN 2073-4409, Vol. 8, no 11, article id 1372Article in journal (Refereed) Published
Abstract [en]

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 (FZD(1-10)), 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 Fc epsilon RI, activation by Fc epsilon RI 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/beta-catenin signaling in mature human mast cells, as revealed by stabilization of beta-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.

Place, publisher, year, edition, pages
MDPI , 2019. Vol. 8, no 11, article id 1372
Keywords [en]
mast cells, Wnt signaling, Wnt-3a, Frizzled, IL-8, CCL8, asthma
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-402237DOI: 10.3390/cells8111372ISI: 000502266700070PubMedID: 31683769OAI: oai:DiVA.org:uu-402237DiVA, id: diva2:1385956
Funder
Swedish Research Council, 2017-04676Swedish Heart Lung FoundationSwedish Foundation for Strategic Research Tore Nilsons Stiftelse för medicinsk forskningLars Hierta Memorial FoundationSwedish Society for Medical Research (SSMF)AstraZenecaScience for Life Laboratory - a national resource center for high-throughput molecular bioscienceSwedish Cancer Society, CAN2017/561Available from: 2020-01-16 Created: 2020-01-16 Last updated: 2020-01-16Bibliographically approved

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