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

Autor(es):Mostrar menos -

Donate, Paula B. ^[1] ; de Lima, Kalil Alves ^[1] ; Peres, Raphael S. ^[1] ; Almeida, Fausto ^[2] ; Fukada, Sandra Y. ^[3] ; Silva, Tarcilia A. ^[4] ; Nascimento, Daniele C. ^[1] ; Cecilio, Nerry T. ^[1] ; Talbot, Jhimmy ^[1] ; Oliveira, Rene D. ^[5] ; Passos, Geraldo A. ^[6] ; Alves-Filho, Jose Carlos ^[1] ; Cunha, Thiago M. ^[1] ; Louzada-Junior, Paulo ^[5] ; Liew, Foo Y. ^[7] ; Cunha, Fernando Q. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Sch Pharmaceut Sci, Dept BioMol Sci, BR-14040903 Sao Paulo, SP - Brazil

^[4] Univ Fed Minas Gerais, Sch Dent, Dept Oral Surg & Pathol, BR-14040903 Belo Horizonte, MG - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, BR-14049900 Ribeirao Preto, SP - Brazil

^[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Mol Immunogenet Grp, BR-14049900 Ribeirao Preto, SP - Brazil

^[7] Univ Glasgow, Glasgow Biomed Res Ctr, gDiv Immunol Infect & Inflammat, Glasgow G12 8TA, Lanark - Scotland

• Tipo de documento: Artigo Científico
• Fonte: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 118, n. 1 JAN 5 2021.
• Citações Web of Science: 1

Resumo

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. miRNA132 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. (AU)

• Processo FAPESP: 12/02438-0 - Identificação dos microRNAs induzidos pela ativação do receptor de hidrocarbonetos de arila (AhR) e de suas funções na patogênese da artrite reumatóide
• Beneficiário: Paula Barbim Donate Yabuta
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs