Diesel exhaust particle-treated human bronchial epithelial cells upregulate Jagged-1 and OX40 ligand in myeloid dendritic cells via thymic stromal lymphopoietin.
Ambient particulate matter, including diesel exhaust particles (DEP), promotes the development of allergic disorders. DEP increase oxidative stress and influence human bronchial epithelial cell (HBEC)-dendritic cell interactions via cytokines, including thymic stromal lymphopoietin (TSLP). Upregulation of TSLP results in Th2 responses. Using primary culture HBEC and human myeloid dendritic cell (mDC) cocultures, we show in this study that DEP upregulation of Th2 responses occurred via HBEC-dependent mechanisms that resulted from oxidative stress. Moreover, DEP-treated HBEC and ambient particulate matter-treated HBEC upregulated OX40 ligand (OX40L) and the Notch ligand Jagged-1 mRNA and expression on mDC. Upregulation of OX40L as well as Jagged-1 on mDC required HBEC and did not occur in the presence of N-acetylcysteine. Furthermore, OX40L and Jagged-1 upregulation was inhibited when HBEC expression of TSLP was silenced. Thus, DEP treatment of HBEC targeted two distinct pathways in mDC that were downstream of TSLP expression. Upregulation of OX40L and Jagged-1 by mDC resulted in mDC-driven Th2 responses. These studies expand our understanding of the mechanism by which ambient pollutants alter mucosal immunity and promote disorders such as asthma.
Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, NY 10016, USA.
Bertram
B
Bleck
Doris B
DB
Tse
Terry
T
Gordon
Mohammad R
MR
Ahsan
Joan
J
Reibman
D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002135:Calcium-Binding Proteins / Q000096:biosynthesis*; D016764:Cell Polarity / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000502:physiology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000096:biosynthesis*; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D053278:OX40 Ligand / Q000096:biosynthesis*; D052638:Particulate Matter / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000633:toxicity; D051880:Receptors, Notch / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D017154:Stromal Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology*; D001335:Vehicle Emissions / Q000633:toxicity*; D000094632:Thymic Stromal Lymphopoietin
D002135:Calcium-Binding Proteins; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D053278:OX40 Ligand; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D001335:Vehicle Emissions; D000094632:Thymic Stromal Lymphopoietin