Determinants of birch pollen allergenicity

• Applicant: Privatdozentin Stefanie Gilles, Ph.D.
• Subject Area: Clinical Immunology and Allergology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 460057662

Background:The induction of a pronounced T helper type 2 (Th2) immune response is a key event in allergic sensitization. We have previously shown that recombinant, highly purified Bet v 1, the major birch pollen allergen, has virtually no sensitizing potential in murine models. By contrast, upon application of the allergen in its natural matrix, i.e. within an aqueous pollen extract, allergic sensitization results even in the absence of external adjuvants. In addition, Bet v 1-depleted birch pollen extracts show a comparable Th2 polarizing potential as Bet v 1-containing extracts. The initial Th2 priming factor within the aqueous pollen extract remains elusive to date. Hypothesis and objectives:The primary objective is to understand how allergic sensitization to birch pollen occurs. We hypothesize that sensitization to Bet v 1 occurs as a consequence of a pre-primed Th2 environment induced by pollen-derived co-factors. By fractionation of birch pollen extracts the complexity of the matrix will be reduced in order to identify Th2-inducing, pollen-derived target compound(s). The immune stimulatory effects of the birch pollen matrix and fractions thereof will be analyzed in vitro on cells involved in innate immunity, i.e. nasal epithelial cells and dendritic cells derived from human donors (allergic and non-allergic). In parallel, an adjuvant-free murine birch pollen allergy model on the background of IL4 (Th2), IFN-γ (Th1) and Foxp3 (Treg) reporter strains will be used to assess in vivo the sensitizing and polarizing activity of candidate birch pollen fractions and -compounds.Expected outcomes and impact:Understanding the mechanism of allergic sensitization to birch pollen and identifying compounds involved in the initial Th2 priming step will help to develop patient-tailored therapeutic approaches and prophylactic treatment. Therefore, our project is of high relevance both for basic immunological research as well as for translational medicine.

• DFG Programme: Research Grants
• International Connection: Austria
• Partner Organisation: Fonds zur Förderung der wissenschaftlichen Forschung (FWF)
• Cooperation Partner: Dr. Lorenz Aglas