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

Author(s)

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

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 8, JUN 16 2017.
• Web of Science Citations: 6

Abstract

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)

• FAPESP's process: 14/12398-1 - Analysis of immunonotulation induced by cigarette smoke in two murine models of chronic allergic pulmonary inflammation
• Grantee: Thayse Regina Bruggemann
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 15/26048-5 - Analysis of dendritic cell and T cell pathway in a murine model of chronic pulmonary allergic inflammation with exposition to cigarette smoke
• Grantee: Thayse Regina Bruggemann
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• FAPESP's process: 14/21395-6 - The role of dendritic cells in the immunomodulation induced by cigarette smoke in a murine model of chronic allergic lung inflammation
• Grantee: Fernanda Magalhães Arantes Costa
• Support Opportunities: Regular Research Grants