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 this study, we showed that mice lacking the main clock transcription factor BMAL1 in myeloid cells have increased lung inflammation demonstrated by higher numbers of eosinophils and increased IL-5 (key pathogenic cytokine in asthma that recruits eosinophils).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 in humans when BMAL1 expression is low.
Zaslona Z, Case S, Early JO, Lalor SJ, McLoughlin RM, Curtis AM*, O’Neill LA* – Both authors contributed equally to this study.
Am J Physiol Lung Cell Mol Physiol. 2017 Mar 23:ajplung.00072.2017. doi: 10.1152/ajplung.00072.2017. [Epub ahead of print]