Considering that ER stress can cause the release of various damage-associated molecular patterns from mitochondria (e.g., mtROS, mitochondrial DNA, ATP, and calcium), which are also potent activators of cytosolic NLRP3 inflammasome [73], interconnection between ER stress, mitochondria, and the NLRP3 inflammasome may play a pivotal role in the pathogenesis of CS-resistant severe type 2 immune response (Fig. 1). This evidence concerns the gene NLRP3 and Cowden syndrome 1.