Olea europaea pollen lipids activate invariant natural killer T cells by upregulating CD1d expression on dendritic cells

J Allergy Clin Immunol. 2013 May;131(5):1393-9.e5. doi: 10.1016/j.jaci.2012.11.014. Epub 2012 Dec 23.

Abstract

Background: Invariant natural killer T (iNKT) cells recognize lipids presented by CD1d and have been implicated in the pathogenesis of allergic asthma. Recognition of plant pollen lipids by iNKT cells and their role in allergic responses are poorly defined.

Objective: Our goal was to investigate whether iNKT cells can be activated by monocyte-derived dendritic cells (DCs) exposed to lipid antigens from Olea europaea.

Methods: DCs generated in vitro were exposed to O europaea pollen grains or lipids isolated from them. Expression of lipid-presenting molecules (CD1), as well as maturation markers (HLA-DR, HLA-I, CD86, and CD80 molecules), on DCs was analyzed. iNKT cell activation after coculture with DCs was evaluated based on expansion, cytokine production, and cytotoxicity tests.

Results: DCs upregulated CD1d and CD86 expression and downregulated CD1a expression after exposure to a whole extract of olive pollen lipids. CD1d and CD1a were regulated at the transcriptional level in a peroxisome proliferator-activated receptor γ activation-dependent manner. Polar lipids, diacylglycerols, free fatty acids, and triacylglycerols isolated from pollen grains upregulate CD1d. The increase in CD1d expression on the DC cell surface induced by polar lipids was not regulated at the RNA level. iNKT cells efficiently recognize DCs treated with the different lipids isolated from olive pollen grains.

Conclusions: Lipids from O europaea pollen upregulate CD1d and CD86 molecules on DCs, which are then able to activate iNKT cells through a CD1d-dependent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / adverse effects
  • Allergens / immunology
  • Antigens, CD1d / biosynthesis*
  • Antigens, CD1d / genetics
  • Antigens, CD1d / physiology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Diglycerides / immunology
  • Humans
  • Immunophenotyping
  • Lipid Metabolism / genetics
  • Lipid Metabolism / immunology*
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology*
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism
  • Olea / adverse effects
  • Olea / immunology*
  • Pollen / adverse effects
  • Pollen / immunology*
  • Up-Regulation / immunology*

Substances

  • Allergens
  • Antigens, CD1d
  • CD1D protein, human
  • Diglycerides