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

Details

• Alternative Title:
  Toxicol Lett
• Personal Author:
  Castañeda, Alejandro R. ; Pinkerton, Kent E. ; Bein, Keith J. ; Magaña-Méndez, Alfonso ; Yang, Houa T. ; Ashwood, Paul ; Vogel, Christoph F. A.
• Description:
  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. PM| 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, PM| 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.
• Subjects:
  Animals Basic Helix-Loop-Helix Transcription Factors Coculture Techniques Cyclooxygenase 2 Cytochrome P-450 CYP1A1 Cytochrome P-450 CYP1B1 Cytokines Dendritic Cells Hep G2 Cells Humans Immunity, Innate Lymphocyte Activation Macrophages Mice, Inbred C57BL Mice, Knockout Particulate Matter Phenotype Receptors, Aryl Hydrocarbon Repressor Proteins Response Elements Signal Transduction Th17 Cells

  More +
• Keywords:
  Aryl Hydrocarbon Receptor (AhR) Dendritic Cells (DCs) Particulate Matter (PM) Polycyclic Aromatic Hydrocarbons (PAHs) Th17 Cells
• Source:
  Toxicol Lett. 292:85-96
• Pubmed ID:
  29689377
• Pubmed Central ID:
  PMC5971007
• Document Type:
  Journal Article
• Funding:
  P01 ES011269/ES/NIEHS NIH HHSUnited States/ ; U54 HD079125/HD/NICHD NIH HHSUnited States/ ; T32 GM099608/GM/NIGMS NIH HHSUnited States/ ; R21 ES025560/ES/NIEHS NIH HHSUnited States/ ; P30 ES023513/ES/NIEHS NIH HHSUnited States/ ; R01 ES019898/ES/NIEHS NIH HHSUnited States/ ; U54 OH007550/OH/NIOSH CDC HHSUnited States/
• Volume:
  292
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:e0e788586f398e04c111736eb023613d9d13651bbeeeb3e2d31c86593b29549b
• Download URL:
  https://stacks.cdc.gov/view/cdc/55086/cdc_55086_DS1.pdf
• File Type:
  [PDF - 1.07 MB ]