Cigarette smoke induces miR-132 in Th17 cells that enhance osteoclastogenesis in inflammatory arthritis

Donate, P. B. et al. (2021) Cigarette smoke induces miR-132 in Th17 cells that enhance osteoclastogenesis in inflammatory arthritis. Proceedings of the National Academy of Sciences of the United States of America, 118(1), e201712011. (doi: 10.1073/pnas.2017120118) (PMID:33443169) (PMCID:PMC7817209)

[img] Text
226419.pdf - Accepted Version

19MB
[img] Text
226419Suppl.pdf - Supplemental Material

3MB

Abstract

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.

Item Type:Articles
Additional Information:This work was supported by grants from the São Paulo Research Foundation (FAPESP, 2012/02438-0 and 2013/08216-2 Center for Research in Inflammatory Disease) and from the University of São Paulo (NAP-DIN, 11.1.21625.01.0).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and Alves-Filho, Dr Jose and Fukada, Dr Sandra
Authors: Donate, P. B., Alves de Lima, K., Peres, R. S., Almeida, F., Fukada, S. Y., Silva, T. A., Nascimento, D. C., Cecilio, N. T., Talbota, J., Oliveira, R. D., Passos, G. A., Alves-Filho, J. C., Cunha, T. M., Louzada-Junior, P., Liew, F. Y., and Cunha, F. Q.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490
Published Online:05 January 2021
Copyright Holders:Copyright © 2021 National Academy of Sciences
First Published:First published in Proceedings of the National Academy of Sciences of the United States of America 118(1):e2017120118
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

University Staff: Request a correction | Enlighten Editors: Update this record