Immunomodulatory effects of aqueous birch pollen extracts and phytoprostanes on primary immune responses in vivo.
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 T(H)2 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 E(1)-phytoprostanes dose-dependently inhibited LPS-induced IL-12p70 of DCs. In addition, Bet-APEs induced a T(H)2 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-gamma secretion from antigen-specific T cells in the draining lymph nodes. In contrast, intranasal E1- and F1-phytoprostanes downregulated both T(H)1 and T(H)2 cytokine production in vivo.


CONCLUSIONS
Pollen release water-soluble factors that display T(H)2-polarizing capacities in vivo independently of E(1)- and F(1)-phytoprostanes.


CONCLUSIONS
Identification of the underlying mechanisms might open new approaches for pharmacologic intervention.
Gutermuth
Jan
J
Division of Environmental Dermatology and Allergy GSF/TUM, GSF National Research Center for Environment and Health, ZAUM-Center for Allergy and Environment, Technische Universität München, Munich, Germany.
Bewersdorff
Mayte
M
Traidl-Hoffmann
Claudia
C
Ring
Johannes
J
Mueller
Martin J
MJ
Behrendt
Heidrun
H
Jakob
Thilo
T
D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D029662:Betula / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000939:Epitopes; D007155:Immunologic Factors; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D028421:Isoprostanes / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D011058:Pollen / Q000737:chemistry*; D012996:Solutions; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D018417:Th1 Cells / Q000166:cytology; D018418:Th2 Cells / Q000166:cytology
D016207:Cytokines; D000939:Epitopes; D007155:Immunologic Factors; D028421:Isoprostanes; D008070:Lipopolysaccharides; D010936:Plant Extracts; D012996:Solutions; D018664:Interleukin-12; D010047:Ovalbumin