Low-dose lipopolysaccharide affects lung allergic responses by regulating Jagged1 expression on antigen-pulsed dendritic cells.

Abstract

BACKGROUND:

Notch signaling pathways govern immune function and the regulation of Th1 and Th2 differentiation. We previously demonstrated essential interactions between Notch on CD4+ T cells and Jagged1 on antigen-presenting cells in Th2 differentiation for the full development of allergen-induced airway hyperresponsiveness (AHR) and allergic airway inflammation.

METHODS:

Bone marrow-derived dendritic cells (BMDCs) were differentiated and incubated with different preparations of ovalbumin (OVA), including lipopolysaccharide (LPS)-depleted and LPS-spiked preparations. In some experiments recipient mice also received soluble Jagged1-Fc in addition to allergen-pulsed BMDCs. Ten days following transfer of BMDCs, mice were exposed to three airway challenges with OVA, and airway responsiveness to inhaled methacholine, airway inflammation and cytokine production were monitored 48 h later. Notch ligand expression was assessed by real-time PCR.

RESULTS:

Induction of Jagged1 expression on antigen-pulsed BMDCs was dependent on low-dose endotoxin. In vivo, transfer of endotoxin-free, antigen-pulsed BMDCs failed to induce AHR or airway eosinophilia on allergen challenge. However, administration of exogenous Jagged1-Fc together with endotoxin-free, allergen-pulsed BMDCs fully restored the responses to allergen challenge.

CONCLUSIONS:

These data demonstrate that LPS regulates the expression of Jagged1 on BMDCs, which is essential for the full development of lung allergic responses.

• Authors: Masakazu Okamoto, Katsuyuki Takeda, Joseph J Lucas, Anthony Joetham, Koji Yasutomo, Erwin W Gelfand
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 157 Issue 1 Pg. 65-72 ( 2012) ISSN: 1423-0097 [Electronic] Switzerland
• PMID: 21912175 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 S. Karger AG, Basel.

Chemical References

• Adaptor Proteins, Signal Transducing
• Antigens
• Calcium-Binding Proteins
• DLL4 protein, mouse
• Intercellular Signaling Peptides and Proteins
• Intracellular Signaling Peptides and Proteins
• Jag1 protein, mouse
• Jagged-1 Protein
• Ligands
• Lipopolysaccharides
• Membrane Proteins
• Receptors, Notch
• Serrate-Jagged Proteins
• Ovalbumin

Topics

• Adaptor Proteins, Signal Transducing
• Adoptive Transfer
• Animals
• Antigens (immunology)
• Asthma (immunology, metabolism)
• Calcium-Binding Proteins (metabolism)
• Dendritic Cells (immunology)
• Disease Models, Animal
• Female
• Intercellular Signaling Peptides and Proteins (metabolism)
• Intracellular Signaling Peptides and Proteins (metabolism)
• Jagged-1 Protein
• Ligands
• Lipopolysaccharides (administration & dosage, immunology)
• Male
• Membrane Proteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Ovalbumin (immunology)
• Receptors, Notch (metabolism)
• Serrate-Jagged Proteins