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Non-allergenic factors from pollen modulate T helper cell instructing notch ligands on dendritic cells
BACKGROUND: Pollen allergens are delivered to epithelial surfaces of the upper respiratory tract in conjunction with multiple endogenous adjuvants. We previously demonstrated pollen-mediated modulation of cytokine and chemokine production of dendritic cells, contributing to a Th2-dominated micromili...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300172/ https://www.ncbi.nlm.nih.gov/pubmed/25610519 http://dx.doi.org/10.1186/s40413-014-0054-8 |
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author | Gilles, Stefanie Beck, Isabelle Lange, Stefan Ring, Johannes Behrendt, Heidrun Traidl-Hoffmann, Claudia |
author_facet | Gilles, Stefanie Beck, Isabelle Lange, Stefan Ring, Johannes Behrendt, Heidrun Traidl-Hoffmann, Claudia |
author_sort | Gilles, Stefanie |
collection | PubMed |
description | BACKGROUND: Pollen allergens are delivered to epithelial surfaces of the upper respiratory tract in conjunction with multiple endogenous adjuvants. We previously demonstrated pollen-mediated modulation of cytokine and chemokine production of dendritic cells, contributing to a Th2-dominated micromilieu. As T helper cell differentiation not only depends on dendritic cell-derived cytokines but also on cell-cell-contact mediated mechanisms, we studied the expression of notch ligands and myeloid differentiation primary response protein 88 (MyD88) in dendritic cells matured in the presence of aqueous birch pollen extracts and pollen-associated E(1)-phytoprostanes. METHODS: Human monocyte-derived dendritic cells were stimulated with aqueous birch pollen extracts in the absence or presence of lipopolysaccharide, and mRNA expression levels of notch ligands delta-1 and −4, jagged-1 and −2 and of myd88 were determined. Regulation of Delta-4 and MyD88 by aqueous pollen extracts was assessed on protein level. The contribution of notch signaling to T helper cell differentiation was analyzed in allogeneic T cell stimulation assays. RESULTS: In immature dendritic cells, stimulation with pollen extracts resulted in an induction of both delta and jagged notch ligands. The lipopolysaccharide-induced up-regulation of delta-1 and −4 and of myd88 was decreased by aqueous pollen extracts, whereas jagged expression was induced. Reduction of Delta-4 and MyD88 by aqueous pollen extracts was confirmed on protein level. The Th2-skewing activity was contained in a fraction of aqueous pollen extracts enriched for molecules <3 kDa and was distinct from the previously identified E(1)-phytoprostanes. Reduction of notch signaling in dendritic cells matured in the presence aqueous pollen extract leads to inhibition of IL-10 and to induction of IL-5 production in naïve T cells differentiated by these dendritic cells. CONCLUSIONS: Pollen derived, non-allergenic factors reduce the dendritic cell’s expression of Th1 instructing Delta-like notch ligands and of MyD88, thereby promoting Th2 skewing of T helper cell responses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40413-014-0054-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4300172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43001722015-01-21 Non-allergenic factors from pollen modulate T helper cell instructing notch ligands on dendritic cells Gilles, Stefanie Beck, Isabelle Lange, Stefan Ring, Johannes Behrendt, Heidrun Traidl-Hoffmann, Claudia World Allergy Organ J Original Research BACKGROUND: Pollen allergens are delivered to epithelial surfaces of the upper respiratory tract in conjunction with multiple endogenous adjuvants. We previously demonstrated pollen-mediated modulation of cytokine and chemokine production of dendritic cells, contributing to a Th2-dominated micromilieu. As T helper cell differentiation not only depends on dendritic cell-derived cytokines but also on cell-cell-contact mediated mechanisms, we studied the expression of notch ligands and myeloid differentiation primary response protein 88 (MyD88) in dendritic cells matured in the presence of aqueous birch pollen extracts and pollen-associated E(1)-phytoprostanes. METHODS: Human monocyte-derived dendritic cells were stimulated with aqueous birch pollen extracts in the absence or presence of lipopolysaccharide, and mRNA expression levels of notch ligands delta-1 and −4, jagged-1 and −2 and of myd88 were determined. Regulation of Delta-4 and MyD88 by aqueous pollen extracts was assessed on protein level. The contribution of notch signaling to T helper cell differentiation was analyzed in allogeneic T cell stimulation assays. RESULTS: In immature dendritic cells, stimulation with pollen extracts resulted in an induction of both delta and jagged notch ligands. The lipopolysaccharide-induced up-regulation of delta-1 and −4 and of myd88 was decreased by aqueous pollen extracts, whereas jagged expression was induced. Reduction of Delta-4 and MyD88 by aqueous pollen extracts was confirmed on protein level. The Th2-skewing activity was contained in a fraction of aqueous pollen extracts enriched for molecules <3 kDa and was distinct from the previously identified E(1)-phytoprostanes. Reduction of notch signaling in dendritic cells matured in the presence aqueous pollen extract leads to inhibition of IL-10 and to induction of IL-5 production in naïve T cells differentiated by these dendritic cells. CONCLUSIONS: Pollen derived, non-allergenic factors reduce the dendritic cell’s expression of Th1 instructing Delta-like notch ligands and of MyD88, thereby promoting Th2 skewing of T helper cell responses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40413-014-0054-8) contains supplementary material, which is available to authorized users. BioMed Central 2015-01-20 /pmc/articles/PMC4300172/ /pubmed/25610519 http://dx.doi.org/10.1186/s40413-014-0054-8 Text en © Gilles et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Original Research Gilles, Stefanie Beck, Isabelle Lange, Stefan Ring, Johannes Behrendt, Heidrun Traidl-Hoffmann, Claudia Non-allergenic factors from pollen modulate T helper cell instructing notch ligands on dendritic cells |
title | Non-allergenic factors from pollen modulate T helper cell instructing notch ligands on dendritic cells |
title_full | Non-allergenic factors from pollen modulate T helper cell instructing notch ligands on dendritic cells |
title_fullStr | Non-allergenic factors from pollen modulate T helper cell instructing notch ligands on dendritic cells |
title_full_unstemmed | Non-allergenic factors from pollen modulate T helper cell instructing notch ligands on dendritic cells |
title_short | Non-allergenic factors from pollen modulate T helper cell instructing notch ligands on dendritic cells |
title_sort | non-allergenic factors from pollen modulate t helper cell instructing notch ligands on dendritic cells |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300172/ https://www.ncbi.nlm.nih.gov/pubmed/25610519 http://dx.doi.org/10.1186/s40413-014-0054-8 |
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