Our body clock drives rhythms in the expression of genes that have a 24-hour periodicity. BMAL1 is a transcription factor, which is a crucial component in the molecular clock. A number of physiological processes, including immune function are modulated by the circadian clock. Asthma is of particular relevance to the area of circadian control of immunity, since it is a disease with very strong clinical evidence demonstrating regulation by circadian variation. Airway hypersensitivity and asthma attacks are more common at night in humans. The molecular basis for this is unknown and no model of asthma in animals with genetic distortion of the molecular clock exists. In our study we have used mice lacking BMAL1 in myeloid cells (BMAL1-LysM-/-) to determine the role of BMAL1 in allergic asthma. Using the Ovalbumin model of allergic asthma we demonstrated that BMAL1-LysM-/- mice have markedly increased asthma features such as increased lung inflammation demonstrated by drastically higher numbers of eosinophils and increased IL-5 levels in the lung and serum. In vitro studies demonstrated that IL-4 as well as LPS treated macrophages from BMAL1-LysM-/- mice have increased pro-inflammatory chemokine expression and M2 markers compared to wild type controls. This suggests that Bmal1 is a potent negative regulator, in myeloid cells in the context of allergic asthma. Our findings might explain the increase in asthma incidents during the night when BMAL1 expression is low.
- myeloid cells
- Copyright © 2017, American Journal of Physiology-Lung Cellular and Molecular Physiology