Nrf2 deficiency in dendritic cells enhances the adjuvant effect of ambient ultrafine particles on allergic sensitization.

Abstract

Particulate matter (PM) is an important risk factor for asthma. Generation of oxidative stress by PM is a major mechanism of its health effects. Transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) mediates antioxidant and phase II enzymes and is essential in protecting against oxidative stress and lung inflammation. We have previously shown that ambient ultrafine particles (UFP) could exert a potent adjuvant effect on allergic sensitization to ovalbumin (OVA) in mice. We hypothesized that Nrf2 deficiency in dendritic cells (DC) could enhance the adjuvant potential of UFP on allergic sensitization. We show that the adjuvant effect of intranasally instilled UFP is significantly enhanced in Nrf2 knockout (Nrf2(-/-)) mice compared with their wild-type (Nrf2(+/+)) counterparts. Under resting conditions, Nrf2(-/-) DC displayed an intrinsic predilection to a T helper 2-favoring cytokine profile characterized by a low level of IL-12p70 and a high level of IL-6 as compared to Nrf2(+/+) DC. Adoptive transfer of OVA/UFP-treated Nrf2(-/-) DC provoked a more severe allergic inflammation in the lung than Nrf2(+/+) DC in the same treatment group. We conclude that Nrf2 deficiency in DC may promote a constitutive immune-polarizing cytokine milieu, which we propose may have contributed to the augmented adjuvant effect of UFP on allergic sensitization.

• Authors: Ning Li, Meiying Wang, Berenice Barajas, Constantinos Sioutas, Marc A Williams, Andre E Nel
• Journal: Journal of innate immunity (J Innate Immun) Vol. 5 Issue 6 Pg. 543-54 ( 2013) ISSN: 1662-8128 [Electronic] Switzerland
• PMID: 23595026 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013 S. Karger AG, Basel.

Chemical References

• Adjuvants, Immunologic
• Interleukin-6
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• Particulate Matter
• Interleukin-12
• Ovalbumin

Topics

• Adjuvants, Immunologic (pharmacology)
• Adoptive Transfer
• Animals
• Asthma (genetics, immunology)
• Cells, Cultured
• Dendritic Cells (immunology, metabolism, transplantation)
• Female
• Interleukin-12 (immunology, metabolism)
• Interleukin-6 (immunology, metabolism)
• Lung (drug effects, immunology, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• NF-E2-Related Factor 2 (deficiency, genetics, immunology)
• Ovalbumin (immunology)
• Particle Size
• Particulate Matter (immunology, pharmacology)
• Th2 Cells (immunology, metabolism)