Ambient particulate matter activates the aryl hydrocarbon receptor in dendritic cells and enhances Th17 polarization

Alejandro R. Castañeda, Kent E Pinkerton, Keith J. Bein, Alfonso Magaña-Méndez, Houa T. Yang, Paul Ashwood, Christoph F.A. Vogel

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The objective of this study was to explore the role of the aryl hydrocarbon receptor (AhR) in ambient particulate matter (PM)-mediated activation of dendritic cells (DCs) and Th17-immune responses in vitro. To assess the potential role of the AhR in PM-mediated activation of DCs, co-stimulation, and cytokine expression, bone marrow (BM)-derived macrophages and DCs from C57BL/6 wildtype or AhR knockout (AhR−/−) mice were treated with PM. Th17 differentiation was assessed via co-cultures of wildtype or AhR−/− BMDCs with autologous naive T cells. PM2.5 significantly induced AhR DNA binding activity to dioxin responsive elements (DRE) and expression of the AhR repressor (AhRR), cytochrome P450 (CYP) 1A1, and CYP1B1, indicating activation of the AhR. In activated (OVA sensitized) BMDCs, PM2.5 induced interleukin (IL)-1β, CD80, CD86, and MHC class II, suggesting enhanced DC activation, co-stimulation, and antigen presentation; responses that were abolished in AhR deficient DCs. DC-T cell co-cultures treated with PM and lipopolysaccharide (LPS) led to elevated IL-17A and IL-22 expression at the mRNA level, which is mediated by the AhR. PM-treated DCs were essential in endowing T cells with a Th17-phenotype, which was associated with enhanced expression of MHC class II and cyclooxygenase (COX)-2. In conclusion, PM enhances DC activation that primes naive T cell differentiation towards a Th17-like phenotype in an AhR-dependent manner.

Original languageEnglish (US)
Pages (from-to)85-96
Number of pages12
JournalToxicology Letters
Volume292
DOIs
StatePublished - Aug 1 2018

Fingerprint

Aryl Hydrocarbon Receptors
Particulate Matter
Dendritic Cells
Polarization
T-cells
Chemical activation
T-Lymphocytes
Coculture Techniques
Phenotype
Dioxins
Interleukin-17
Macrophages
Antigen Presentation
Cyclooxygenase 2
Interleukin-1
Cell culture
Cytochrome P-450 Enzyme System
Lipopolysaccharides
Cell Differentiation
Bone

Keywords

  • Aryl hydrocarbon receptor (AhR)
  • Dendritic cells (DCs)
  • Particulate matter (PM)
  • Polycyclic aromatic hydrocarbons (PAHs)
  • Th17 cells

ASJC Scopus subject areas

  • Toxicology

Cite this

Ambient particulate matter activates the aryl hydrocarbon receptor in dendritic cells and enhances Th17 polarization. / Castañeda, Alejandro R.; Pinkerton, Kent E; Bein, Keith J.; Magaña-Méndez, Alfonso; Yang, Houa T.; Ashwood, Paul; Vogel, Christoph F.A.

In: Toxicology Letters, Vol. 292, 01.08.2018, p. 85-96.

Research output: Contribution to journalArticle

Castañeda, Alejandro R. ; Pinkerton, Kent E ; Bein, Keith J. ; Magaña-Méndez, Alfonso ; Yang, Houa T. ; Ashwood, Paul ; Vogel, Christoph F.A. / Ambient particulate matter activates the aryl hydrocarbon receptor in dendritic cells and enhances Th17 polarization. In: Toxicology Letters. 2018 ; Vol. 292. pp. 85-96.
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AU - Bein, Keith J.

AU - Magaña-Méndez, Alfonso

AU - Yang, Houa T.

AU - Ashwood, Paul

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