Details
- Autor(en) / Beteiligte
- Titel
- Ambient particulate matter activates the aryl hydrocarbon receptor in dendritic cells and enhances Th17 polarization
- Ist Teil von
- Toxicology letters, 2018-08, Vol.292, p.85-96
- Ort / Verlag
- Netherlands: Elsevier B.V
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- [Display omitted] •Air pollution PM can shape CD4+ T cell immune responses via the AhR in DCs.•PAHs in PM activate the AhR in DCs.•PM enhances DC activation by increasing CD80, CD86, and MHC class II expression.•DCs prime T cell differentiation towards a Th17-like phenotype in an AhR-dependent manner.•DCs are essential in Th17-like differentiation as PAHs act via the AhR in DCs, not T cells. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0378-4274eISSN: 1879-3169DOI: 10.1016/j.toxlet.2018.04.020Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5971007
- Format
- –
- Schlagworte
- Animals, Aryl hydrocarbon receptor (AhR), Basic Helix-Loop-Helix Transcription Factors - agonists, Basic Helix-Loop-Helix Transcription Factors - deficiency, Basic Helix-Loop-Helix Transcription Factors - genetics, Basic Helix-Loop-Helix Transcription Factors - metabolism, Coculture Techniques, Cyclooxygenase 2 - genetics, Cyclooxygenase 2 - metabolism, Cytochrome P-450 CYP1A1 - genetics, Cytochrome P-450 CYP1A1 - metabolism, Cytochrome P-450 CYP1B1 - genetics, Cytochrome P-450 CYP1B1 - metabolism, Cytokines - genetics, Cytokines - metabolism, Dendritic cells (DCs), Dendritic Cells - drug effects, Dendritic Cells - immunology, Dendritic Cells - metabolism, Hep G2 Cells, Humans, Immunity, Innate - drug effects, Lymphocyte Activation - drug effects, Macrophages - drug effects, Macrophages - immunology, Macrophages - metabolism, Mice, Inbred C57BL, Mice, Knockout, Particulate matter (PM), Particulate Matter - toxicity, Phenotype, Polycyclic aromatic hydrocarbons (PAHs), Receptors, Aryl Hydrocarbon - agonists, Receptors, Aryl Hydrocarbon - deficiency, Receptors, Aryl Hydrocarbon - genetics, Receptors, Aryl Hydrocarbon - metabolism, Repressor Proteins - genetics, Repressor Proteins - metabolism, Response Elements, Signal Transduction - drug effects, Th17 cells, Th17 Cells - drug effects, Th17 Cells - immunology, Th17 Cells - metabolism