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. 2014 Sep;134(3):521–529. doi: 10.1016/j.jaci.2014.04.015

Table II.

Overview of lipid mediators and their mechanisms of action

Lipids Source Experimental setting Effects Mechanism of action References
Microbial lipids in pollen grains Extract of gram-positive bacteria, Bacillus cereus and Bacillus subtilis, from timothy (Phleum pratense) pollen grains Human immature DCs ↑ Maturation markers
↑ IL-6, IL12 p40, and TNF-α in allergic donors
Adjuvant activity by enhancing maturation of DCs and induction of TH1-, TH2-, and TH17-mediated allergic inflammation Heydenreich et al31
DC/naive T-cell coculture Allergen-specific proliferation and ↑ production of IL-4, IL-10, IL-13, IL-17, IL-22, and IFN-γ
Ryegrass (Lolium perenne) pollen extracts with LPS content >5000 EU/mL containing bacterial lipopeptides and CpG motifs Human PBMCs ↑ IFN-γ+ and IL-4+ cells;
↓ CD4+ Foxp3hi Treg cells
↑ IFN-γ, TNF-α ,IL-5, IL-10
TH1- and TH2-biased proinflammatory response with reduction in Treg cell numbers Mittag et al32
HEK293 cells expressing TLRs Activation of TLR4, TLR2, and TLR9
Glycolipid α-glycuronosylceramides BALB/c mice immunized with OVA and α-galactosylceramide ↑ Airway hyperreactivity
↑ Airway eosinophils
↑ IgE and TH2 cytokines
α-Glycuronosylceramides act as adjuvants binding to CD1d and activating Vα14 iNKT cells Kim at al43
Mouse in vivo studies Local activation of natural killer T cells and release of IL-4 and IFN-γ followed by activation of DCs and allergen-specific CD4+ TH2 cells Scanlon et al44
Pollen lipids Phospatidylcholine and phospatidylethanolamine from cypress pollen grains (Cupressus arizonica and Cupressus sempervirens) Autologous DCs and T-cell lines from patients with cypress pollen allergy Proliferation of pollen lipid–specific TH2 cells secreting IL-4 and IFN-γ
↑ Lipid-specific IgE
CD1a- and CD1d-mediated recognition of pollen lipids by T cells Agea et al33
Total lipid fractions from olive pollen (Olea europaea) PBMCs from healthy donors ↑ IL-4 and IFN-γ
↑ Expression of CD1d on DCs
↓ Expression of CD1a
Activation of iNKT cells in a CD1d-dependent way through PPARγ Abos-Gracia et al34
PALMs Aqueous and lipid extracts from grass (Phleum pratense) and birch (Betula alba) pollen Human neutrophils and eosinophils Attraction and activation of neutrophils and eosinophils
↑ CD11b
Chemoattractant activity, which generates a TH2-promoting micromilieu Plotz et al35 Traidl-Hoffmann et al36
Aqueous birch (Betula alba) pollen extract Human LPS-maturated MoDCs Inhibition of LPS-induced production of the TH1-attracting chemokines CXCL10 and CCL5
↑ Release of CCL22
Mariani et al38
Phytoprostanes E1 Human LPS-maturated MoDCs Inhibition of LPS-induced IL-12 p70 through inhibition of PPARγ signaling and consecutive TH2 polarization Polarization of naive T cells to TH2 type by inhibiting DCs to produce TH1 cytokine IL12 p70 or IL-6 Gilles et al37 Traidl-Hoffmann et al39
Phytoprostanes E1 slanDCs Inhibition of LPS-induced IL-12 p70 and IL-6 Gilles et al40
Low-molecular-weight nonprotein factors from Betula alba LPS-stimulated-slanDCs Inhibition of LPS-induced surface expression of T-cell costimulatory markers CD80 and CD40 and chemokine receptor CCR7 Modulation of a native human DC subset on the level of cytokine production, costimulation, and ensuing T-cell response Gilles et al40
Dietary MCTs Peanut butter Oral sensitization of naive C3H/HeJ mice with peanut butter proteins with MCTs IgG-dependent anaphylaxis after systemic challenge and IgE-dependent anaphylaxis after oral challenge;
Promote TH2 cytokine responses in splenocytes
Stimulation of TH2 responses by affecting antigen absorption and availability Li et al41
Sphingolipids Cow's milk PBMCs from children with cow's milk allergy or eosinophilic esophagitis Sphingolipid-dependent iNKT cell proliferation and secretion of TH2 cytokines IL-4, IL-5, and IL-13 Activation of peripheral blood iNKT cells to produce TH2 cytokines and eosinophil-mediated inflammation Jyonouchi et al26, 42

Foxp3, Forkhead box protein 3; LTA, lipoteichoic acid; MCT, medium-chain triglyceride; OVA, ovalbumin; PPARγ, peroxisome proliferator-activated receptor γ; slanDC, 6-sulfo LacNac+ dendritic cell; Treg, regulatory T.