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.