Cigarette Smoke Increases CD8 alpha(+) Dendritic Cells in an Ovalbumin-Induced Airway Inflammation

Autor(es)

Bruggemann, Thayse Regina ; Fernandes, Paula ; Oliveira, Luana de Mendonca ; Sato, Maria Notomi ; Martins, Mlton de Arruda ; Arantes-Costa, Fernanda Magalhaes

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 8, JUN 16 2017.
• Citações Web of Science: 6

Resumo

Asthma is an allergic lung disease and, when associated to cigarette smoke exposition, some patients show controversial signs about lung function and other inflammatory mediators. Epidemiologic and experimental studies have shown both increasing and decreasing inflammation in lungs of subjects with asthma and exposed to cigarette smoke. Therefore, in this study, we analyzed how cigarette smoke affects pro-inflammatory and anti-inflammatory mediators in a murine model of allergic pulmonary inflammation. We sensitized Balb/c mice to ovalbumin (OVA) with two intraperitoneal injections. After sensitization, the animals were exposed to cigarette smoke twice a day, 30 min per exposition, for 12 consecutive days. In order to drive the cell to the lungs, four aerosol challenges were performed every 48 h with the same allergen of sensitization. OVA sensitization and challenge developed pulmonary Th2 characteristic response with increased airway responsiveness, remodeling, increased levels of IgE, interleukin (IL)-4, and IL-13. Cigarette smoke, unexpectedly, reduced the levels of IL-4 and IL-13 and simultaneously decreased anti-inflammatory cytokines as IL-10 and transforming growth factor (TGF)-alpha in sensitized and challenged animals. OVA combined with cigarette smoke exposition decreased the number of eosinophils in bronchoalveolar lavage and increased the number of neutrophils in lung. The combination of cigarette smoke and lung allergy increased recruitment of lymphoid dendritic cells (DCs) into lymph nodes, which may be the leading cause to an increase in number and activation of CD8(+) T cells in lungs. In addition, lung allergy and cigarette smoke exposure decreased an important regulatory subtype of DC such as plasmacytoid DC as well as its activation by expression of CD86, PDL2, and ICOSL, and it was sufficient to decrease T regs influx and anti-inflammatory cytokines release such as IL-10 and TGF-alpha but not enough to diminish the structural changes. In conclusion, we observed, in this model, that OVA sensitization and challenge combined with cigarette smoke exposure leads to mischaracterization of the Th2 response of asthma by decreasing the number of eosinophils, IL-4, and IL-13 and increasing number of neutrophils, which is related to the increased number of CD8 alpha(+) DCs and CD8+ T cells as well as reduction of the regulatory cells and its released cytokines. (AU)

• Processo FAPESP: 14/12398-1 - Análise do perfil inflamatório na imunorregulação induzida pela fumaça do cigarro em dois modelos murinos de inflamação pulmonar alérgica crônica
• Beneficiário: Thayse Regina Bruggemann
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 15/26048-5 - Análise da interação entre células dendríticas e células T em um modelo murino de inflamação pulmonar alérgica crônica com exposição à fumaça de cigarro
• Beneficiário: Thayse Regina Bruggemann
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto
• Processo FAPESP: 14/21395-6 - O papel das células dendríticas na imunorregulação induzida pela fumaça do cigarro em um modelo murino de inflamação pulmonar alérgica crônica
• Beneficiário: Fernanda Magalhães Arantes Costa
• Modalidade de apoio: Auxílio à Pesquisa - Regular