Immunomodulatory effects of aqueous birch pollen extracts and phytoprostanes on primary immune responses in vivo

BackgroundWe recently demonstrated that pollen not only function as allergen carriers but also as rich sources of bioactive lipids, such as phytoprostanes, that modulate human dendritic cell (DC) function in a way that results in an enhanced TH2 polarization in vitro.ObjectiveHere we analyzed the immunomodulatory capacities of Betula alba (white birch) aqueous pollen extracts (Bet-APEs) and pollen-associated phytoprostanes in the murine system in vitro and in vivo.MethodsDC function was analyzed in vitro by using BALB/c bone marrow–derived DCs. T-cell responses were analyzed with DO11.10 peptide 323-339 from chicken ovalbumin (OVA)–specific CD4 T cells as responder cells. For in vivo studies, OVA-specific CD4 T cells were adoptively transferred into BALB/c mice. Twenty-four hours later, mice were challenged by means of intranasal application of OVA in the absence or presence of Bet-APEs or phytoprostanes. Polarization of T-cell responses in vivo was analyzed in draining lymph node cells.ResultsIn vitro Bet-APEs and E1–phytoprostanes dose-dependently inhibited LPS-induced IL-12p70 of DCs. In addition, Bet-APEs induced a TH2 polarization in vitro. Similarly, intranasal instillation of Bet-APEs in vivo, together with the antigen, lead to increased IL-4, IL-5, and IL-13 secretion and decreased IFN-γ secretion from antigen-specific T cells in the draining lymph nodes. In contrast, intranasal E1- and F1–phytoprostanes downregulated both TH1 and TH2 cytokine production in vivo.ConclusionPollen release water-soluble factors that display TH2-polarizing capacities in vivo independently of E1- and F1–phytoprostanes.Clinical implicationsIdentification of the underlying mechanisms might open new approaches for pharmacologic intervention.