Fig. 1

Th2-autoinflammatory pathways interaction: (A) Activation of the inflammasome genes including NLRP3, Pyrine, LPIN-2 transform inactive pro-IL-1b and pro-IL-18 into their active forms which lead to enhanced Th2 differentiation. IL-1b induce allergic lung inflammation via different effector cells, while IL-18 has context-dependent effect as it can constrain antiparasitic responses and also induce IL-13 in natural killer (NK) cells and basophils which contribute to the innate part of type 2 immune response. NLRP3 has both inflammasome-dependent and independent pathways which act as brake on type 2 responses. Pyrine has no major role in type 2 immune response, it lessens allergic inflammation by inhibiting NF-kB activation. (B) NF-kB signaling is known to play a role in Th2 differentiation and IgE production. TNFa receptors act as major activators to NF-kB pathway, enhances Th2 and Th9 differentiation, and the effect of IL-4 on eosinophils which may worsen asthma. NOD2 enhances TSLP, ILC2, and eosinophilic activation, and constitutive activation of NF-kB leading to upregulation of proinflammatory cytokines. NF-kB, nuclear factor kappa B; IL-1; TRAPS, periodic necrosis factor associated receptor 1; FMF: familiar Mediterranean fever; CAPS: cryopyrin-associated periodic syndrome