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Influenza virus infections have been a persistent threat to society, causing up to 650,000 respiratory deaths annually world-wide. The United States alone suffered 80,000 influenza-related deaths d...

SummaryBackground The prevalence of asthma in the elderly is increasing and associated with higher mortality than in children or young adults. However, the effects of age on the development and character of allergic asthma have been understudied. It has been suggested that mixed Th2/Th17 responses cause more severe forms of asthma, but the role of Th17 response in allergic airway disease and aging is not well understood. Objective To investigate age-dependent characteristics and Th17 immune response in allergic airway disease in a murine house dust mite (HDM)-allergen model. Methods Twelve-week-old and 15-month-old male BALB/c mice were sensitized and challenged with HDM. Bronchoalveolar lavage fluid (BALF), airway inflammation and hyperresponsiveness (AHR), serum immunoglobulin and splenic T cells were assessed. Age-related T cell activation was analyzed in a co-culture with bone marrow-derived dendritic cells (BMDC) and splenic CD4+T cells from young and old mice. Results Features of allergic airway disease such as mucous cell hyperplasia, infiltration of airway eosinophils and lymphocytes, Th2 cytokine expression and serum IgG1 levels were greater in old compared to young mice. In contrast to the more marked inflammatory/immune responses to HDM in old mice, AHR was greater in young HDM-treated mice. Only the old mice developed airway neutrophil infiltration and a Th17 immune response upon HDM exposure, with increases in BALF cytokines IL-17A and KC, and Th17 cytokine producing T cells in the spleen. Stimulation of CD4+T cells and BMDC co-cultures with HDM, resulted in an enhanced Th17 cytokine response in cells isolated from old mice. Conclusions and Clinical Relevance Our findings in mice suggest that the severity and character of allergic airway disease are age dependent, with a bias towards a Th17 immune response with aging. Elderly, asthmatics may be prone to develop severe allergic airway inflammation with a mixed Th2/Th17 immune response.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor activated by cell stresses, such as reactive oxygen species and electrophilic stimuli. Upon activation Nrf2 accumulates within the nucleus, where it induces transcription of its target genes. In mice a growing number of studies indicate a role for Nrf2 in the development of immune mediated diseases, including inflammatory diseases such as allergy and autoimmunity. Recently, we have shown that the Nrf2 activator, tBHQ, modulates early events of T cell activation in human Jurkat T cells. This is evidenced by a marked inhibition of the cytokine IL-2, as well as a reduction in the expression of CD25, the high-affinity subunit of the IL-2 receptor. The suppression of IL-2 by tBHQ correlates with a concurrent suppression of the transcription factor NFκB, a transcription factor known to have multiple binding sites within the IL-2 promoter. Although we have shown that the synthetic food additive tBHQ modulates the early events of Jurkat ...

Hypoxia-inducible factor-1α (HIF-1α) is activated in hepatic stellate cells (HSCs) by hypoxia, and regulates genes important for tissue repair. Whether HIF-1α is activated in HSCs after acute injur...

Nrf2 is a transcription factor that is activated by cell stress, such as the presence of oxidative compounds. After activation and translocation to the nucleus, Nrf2 binds to and induces the transc...