Chronic allergy signaling: is it all stressed-out mitochondria?

Abstract

Allergic diseases in general, and chronic allergic inflammation in particular, are on the rise in the United States and other developed countries. The idea of chronic allergic disease as a chronic type 2 immune response has been around for several decades. However, data suggest that other mechanisms may be important in chronic disease. Therefore, we believe it is time for a paradigm shift in understanding the mechanistic causes of disease symptoms in these diseases. In this review, we have avoided the classic canonical pathways and focused on the emerging idea that oxidative stress, changes in immuno-metabolism, mitochondrial dysfunction, and epigenetic changes (particularly microRNA profile) may be working concurrently or synergistically to potentiate allergic disease symptoms. Furthermore, we have addressed how the epidemic of obesity exacerbates allergic disease via the dysregulation of the aforementioned factors.

Keywords: homeostasis; metabolism; microRNA; mitochondrial dysfunction; obesity.

Figure 1.. Potential role of mitochondrial stress in chronic allergic disease.

The cartoon demonstrates the impact of allergen exposure on airway epithelial cell mitochondria (top panel) and subsequent mitochondrial dysfunction that may drive symptoms of chronic allergic disease. The bottom panel shows that obesity through a high saturated fatty acid diet drives similar stress responses in the mitochondria of macrophages and other phagocytic cells, and this may lead to the exacerbation of allergic diseases. ROS, reactive oxygen species.