Proceedings of the National Academy of Sciences - PNAS, 2021-01, Vol.118 (1), p.1-8
2021
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- Autor(en) / Beteiligte
- Titel
- Cigarette smoke induces miR-132 in Th17 cells that enhance osteoclastogenesis in inflammatory arthritis
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2021-01, Vol.118 (1), p.1-8
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2021
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint destruction and severe morbidity. Cigarette smoking (CS) can exacerbate the incidence and severity of RA. Although Th17 cells and the Aryl hydrocarbon receptor (AhR) have been implicated, the mechanism by which CS induces RA development remains unclear. Here, using transcriptomic analysis, we show that microRNA-132 is specifically induced in Th17 cells in the presence of either AhR agonist or CS-enriched medium. miRNA-132 thus induced is packaged into extracellular vesicles produced by Th17 and acts as a proinflammatory mediator increasing osteoclastogenesis through the down-regulation of COX2. In vivo, articular knockdown of miR-132 in murine arthritis models reduces the number of osteoclasts in the joints. Clinically, RA patients express higher levels of miR-132 than do healthy individuals. This increase is further elevated by cigarette smoking. Together, these results reveal a hitherto unrecognized mechanism by which CS could exacerbate RA and further advance understanding of the impact of environmental factors on the pathogenesis of chronic inflammatory diseases.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.2017120118Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7817209
- Format
- –
- Schlagworte
- Adult, Aged, Animal models, Animals, Aromatic compounds, Arthritis, Arthritis, Experimental - pathology, Arthritis, Rheumatoid - genetics, Arthritis, Rheumatoid - metabolism, Arthritis, Rheumatoid - pathology, Basic Helix-Loop-Helix Transcription Factors - metabolism, Biological Sciences, Biomedical materials, Cigarette smoke, Cigarette smoking, Cigarette Smoking - adverse effects, Cyclooxygenase-2, Down-regulation, Environmental factors, Environmental impact, Female, Helper cells, Humans, Inflammatory diseases, Joint diseases, Lymphocytes T, Male, Mice, Mice, Inbred C57BL, MicroRNAs, MicroRNAs - genetics, MicroRNAs - metabolism, Middle Aged, miRNA, Morbidity, Osteoclastogenesis, Osteoclasts, Osteoclasts - metabolism, Osteogenesis - drug effects, Osteogenesis - physiology, Pathogenesis, Receptors, Aryl Hydrocarbon - metabolism, Rheumatoid arthritis, Ribonucleic acid, RNA, Smoke, Smoking, Th17 Cells - drug effects, Th17 Cells - metabolism, Tobacco Smoke Pollution - adverse effects