title: Non-allergenic factors from pollen modulate T helper cell instructing notch ligands on dendritic cells.
abstract: 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 E1-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 E1-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.
authors.affiliation: Institute of Environmental Medicine, UNIKA-T, medical faculty of the Technische Universität München, Augsburg, Germany ; CK-Care, Christine Kühne Center for Allergy Research and Education, Davos-Wolfgang, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Gilles
authors.affiliation: Institute of Environmental Medicine, UNIKA-T, medical faculty of the Technische Universität München, Augsburg, Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Beck
authors.affiliation: Institute of Environmental Medicine, UNIKA-T, medical faculty of the Technische Universität München, Augsburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lange
authors.affiliation: Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Ring
authors.affiliation: ZAUM - Center for Allergy and Environment, Helmholtz Center and Technische Universität München, Munich, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Behrendt
authors.affiliation: Institute of Environmental Medicine, UNIKA-T, medical faculty of the Technische Universität München, Augsburg, Germany ; CK-Care, Christine Kühne Center for Allergy Research and Education, Davos-Wolfgang, Switzerland ; Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Traidl-Hoffmann
keywords: Dendritic cells; MyD88; Notch ligands; Pollen