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Background: We 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. Objective: Here 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. Methods: DC 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. Results: In 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. Conclusion: Pollen release water-soluble factors that display TH2-polarizing capacities in vivo independently of E1- and F1–phytoprostanes. Clinical implications: Identification of the underlying mechanisms might open new approaches for pharmacologic intervention. [Copyright &y& Elsevier]

Mast cells are pivotal effector cells in IgE-mediated allergic inflammatory diseases. Central for mast cell activation are signals from the IgE receptor FCεRI, which induce cell degranulation with the release of preformed mediators and de novo synthesis of proinflammatory leukotrienes and cytokines. How these individual mast cell responses are differentially controlled is still unresolved. We identify B cell lymphoma 10 (Bcl10) and mucosa-associated lymphoid tissue 1 (Malt1) as novel key regulators of mast cell signaling. Mice deficient for either protein display severely impaired IgE-dependent late phase anaphylactic reactions. Mast cells from these animals neither activate nuclear factor κB (NF-κB) nor produce tumor necrosis factor α or interleukin 6 upon FcεRI ligation even though proximal signaling, degranulation, and leukotriene secretion are normal. Thus, Bcl10 and Malt1 are essential positive mediators of FcεRI-dependent mast cell activation that selectively uncouple NF-κB-induced proinflammatory cytokine production from degranulation and leukotriene synthesis. [ABSTRACT FROM AUTHOR]

Allergic contact dermatitis and atopic eczema are common skin diseases that seriously affect the patient''s quality of life. Disease models are important for understanding the complex disease mechanisms and for developing better therapeutic strategies. In this review, the latest disease models for studying the pathophysiology and treatment modalities, as well as models used for predictive testing of substances with contact sensitizing potential are discussed. [Copyright &y& Elsevier]