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

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.