Smoking-induced aggravation of experimental arthritis is dependent of aryl hydrocarbon receptor activation in Th17 cells

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dc.contributor.authorTalbot, Jhimmy
dc.contributor.authorPeres, Raphael S
dc.contributor.authorPinto, Larissa G
dc.contributor.authorOliveira, Rene D R
dc.contributor.authorLima, Kalil A
dc.contributor.authorDonate, Paula B
dc.contributor.authorSilva, Jaqueline R
dc.contributor.authorRyffel, Bernard
dc.contributor.authorCunha, Thiago M
dc.contributor.authorAlves-Filho, José C
dc.contributor.authorLiew, Foo Y
dc.contributor.authorLouzada-Junior, Paulo
dc.contributor.authorde Queiroz Cunha, Fernando
dc.date.accessioned2018-07-06T09:48:58Z
dc.date.available2018-07-06T09:48:58Z
dc.date.issued2018-06-08
dc.date.updated2018-06-10T03:38:40Z
dc.description.abstractBackground Epidemiologic studies have highlighted the association of environmental factors with the development and progression of autoimmune and chronic inflammatory diseases. Among the environmental factors, smoking has been associated with increased susceptibility and poor prognosis in rheumatoid arthritis (RA). However, the immune and molecular mechanism of smoking-induced arthritis aggravation remains unclear. The transcription factor aryl hydrocarbon receptor (AHR) regulates the generation of Th17 cells, CD4 T cells linked the development of autoimmune diseases. AHR is activated by organic compounds including polycyclic aromatic hydrocarbons (PAHs), which are environmental pollutants that are also present in cigarette smoke. In this study, we investigated the role of AHR activation in the aggravation of experiment arthritis induced by exposure to cigarette smoke. Methods Mice were exposed to cigarette smoke during the developmental phase of antigen-induced arthritis and collagen-induced arthritis to evaluate the effects of smoking on disease development. Aggravation of articular inflammation was assessed by measuring neutrophil migration to the joints, increase in articular hyperalgesia and changes in the frequencies of Th17 cells. In vitro studies were performed to evaluate the direct effects of cigarette smoke and PAH on Th17 differentiation. We also used mice genetically deficient for AHR (Ahr KO) and IL-17Ra (Il17ra KO) to determine the in vivo mechanism of smoking-induced arthritis aggravation. Results We found that smoking induces arthritis aggravation and increase in the frequencies of Th17 cells. The absence of IL-17 signaling (Il17ra KO) conferred protection to smoking-induced arthritis aggravation. Moreover, in vitro experiments showed that cigarette smoke can directly increase Th17 differentiation of T cells by inducing AHR activation. Indeed, Ahr KO mice were protected from cigarette smoke-induced arthritis aggravation and did not display increase in TH17 frequencies, suggesting that AHR activation is an important mechanism for cigarette smoke effects on arthritis. Finally, we demonstrate that PAHs are also able to induce arthritis aggravation. Conclusions Our data demonstrate that the disease-exacerbating effects of cigarette smoking are AHR dependent and environmental pollutants with AHR agonist activity can induce arthritis aggravation by directly enhancing Th17 cell development.
dc.identifier.apacitationTalbot, J., Peres, R. S., Pinto, L. G., Oliveira, R. D. R., Lima, K. A., Donate, P. B., ... de Queiroz Cunha, F. (2018). Smoking-induced aggravation of experimental arthritis is dependent of aryl hydrocarbon receptor activation in Th17 cells. <i>Arthritis Research & Therapy</i>, http://hdl.handle.net/11427/28278en_ZA
dc.identifier.chicagocitationTalbot, Jhimmy, Raphael S Peres, Larissa G Pinto, Rene D R Oliveira, Kalil A Lima, Paula B Donate, Jaqueline R Silva, et al "Smoking-induced aggravation of experimental arthritis is dependent of aryl hydrocarbon receptor activation in Th17 cells." <i>Arthritis Research & Therapy</i> (2018) http://hdl.handle.net/11427/28278en_ZA
dc.identifier.citationTalbot, J., Peres, R. S., Pinto, L. G., Oliveira, R. D., Lima, K. A., Donate, P. B., ... & Liew, F. Y. (2018). Smoking-induced aggravation of experimental arthritis is dependent of aryl hydrocarbon receptor activation in Th17 cells. Arthritis research & therapy, 20(1), 119.
dc.identifier.ris TY - Journal Article AU - Talbot, Jhimmy AU - Peres, Raphael S AU - Pinto, Larissa G AU - Oliveira, Rene D R AU - Lima, Kalil A AU - Donate, Paula B AU - Silva, Jaqueline R AU - Ryffel, Bernard AU - Cunha, Thiago M AU - Alves-Filho, José C AU - Liew, Foo Y AU - Louzada-Junior, Paulo AU - de Queiroz Cunha, Fernando AB - Background Epidemiologic studies have highlighted the association of environmental factors with the development and progression of autoimmune and chronic inflammatory diseases. Among the environmental factors, smoking has been associated with increased susceptibility and poor prognosis in rheumatoid arthritis (RA). However, the immune and molecular mechanism of smoking-induced arthritis aggravation remains unclear. The transcription factor aryl hydrocarbon receptor (AHR) regulates the generation of Th17 cells, CD4 T cells linked the development of autoimmune diseases. AHR is activated by organic compounds including polycyclic aromatic hydrocarbons (PAHs), which are environmental pollutants that are also present in cigarette smoke. In this study, we investigated the role of AHR activation in the aggravation of experiment arthritis induced by exposure to cigarette smoke. Methods Mice were exposed to cigarette smoke during the developmental phase of antigen-induced arthritis and collagen-induced arthritis to evaluate the effects of smoking on disease development. Aggravation of articular inflammation was assessed by measuring neutrophil migration to the joints, increase in articular hyperalgesia and changes in the frequencies of Th17 cells. In vitro studies were performed to evaluate the direct effects of cigarette smoke and PAH on Th17 differentiation. We also used mice genetically deficient for AHR (Ahr KO) and IL-17Ra (Il17ra KO) to determine the in vivo mechanism of smoking-induced arthritis aggravation. Results We found that smoking induces arthritis aggravation and increase in the frequencies of Th17 cells. The absence of IL-17 signaling (Il17ra KO) conferred protection to smoking-induced arthritis aggravation. Moreover, in vitro experiments showed that cigarette smoke can directly increase Th17 differentiation of T cells by inducing AHR activation. Indeed, Ahr KO mice were protected from cigarette smoke-induced arthritis aggravation and did not display increase in TH17 frequencies, suggesting that AHR activation is an important mechanism for cigarette smoke effects on arthritis. Finally, we demonstrate that PAHs are also able to induce arthritis aggravation. Conclusions Our data demonstrate that the disease-exacerbating effects of cigarette smoking are AHR dependent and environmental pollutants with AHR agonist activity can induce arthritis aggravation by directly enhancing Th17 cell development. DA - 2018-06-08 DB - OpenUCT DP - University of Cape Town J1 - Arthritis Research & Therapy LK - https://open.uct.ac.za PB - University of Cape Town PY - 2018 T1 - Smoking-induced aggravation of experimental arthritis is dependent of aryl hydrocarbon receptor activation in Th17 cells TI - Smoking-induced aggravation of experimental arthritis is dependent of aryl hydrocarbon receptor activation in Th17 cells UR - http://hdl.handle.net/11427/28278 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s13075-018-1609-9
dc.identifier.urihttp://hdl.handle.net/11427/28278
dc.identifier.vancouvercitationTalbot J, Peres RS, Pinto LG, Oliveira RDR, Lima KA, Donate PB, et al. Smoking-induced aggravation of experimental arthritis is dependent of aryl hydrocarbon receptor activation in Th17 cells. Arthritis Research & Therapy. 2018; http://hdl.handle.net/11427/28278.en_ZA
dc.language.isoen
dc.publisherBioMed Central
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rights.holderThe Author(s).
dc.sourceArthritis Research & Therapy
dc.source.urihttps://arthritis-research.biomedcentral.com/
dc.subject.otherRheumatoid arthritis
dc.subject.otherCigarette smoke
dc.subject.otherInflammation
dc.subject.otherPolycyclic aromatic hydrocarbons
dc.subject.otherTh17
dc.titleSmoking-induced aggravation of experimental arthritis is dependent of aryl hydrocarbon receptor activation in Th17 cells
dc.typeJournal Article
uct.type.filetypeText
uct.type.filetypeImage
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