In conclusion, the present study demonstrates that a TLR2-melatonin feedback loop regulates the activation of NLRP3 inflammasome in allergic airway inflammation, and suppression of melatonin synthesis by TLR2 activation in turn results in the loss of its inhibitory effect on the TLR2 signaling (Figure 7). This important endogenous regulatory feedback loop may drive the onset of allergic airway inflammation, and melatonin may be a promising therapeutic medicine for airway inflammatory disease such as asthma. The present study used OVA model, which has been the most widely used pre-clinical allergic asthma model and recapitulates many of the hallmarks of allergic asthma in humans, however, bio-models offer other allergen-induced allergic model, such as house dust mite (HDM), Alternaria, papain and IL-33, with each mimicking the major features of human asthma. When OVA, HDM, or Alternaria was given via inhalation or intranasally, each of them can be recognized and sensed by TLRs reportedly, especially TLR2 (40). Similarly, intranasally given IL-33 is reported can induce direct stimulation of TLR2 on ILC2s (39). However, papain, which is homologous of HDM-derived Der p1, activates innate immune responses in a manner distinct from that of PAPMs and can induce production of an alarmin IL-33 (63). We hypothesize our findings may be also applicable to other allergens–induced allergic airway inflammation models in which TLR2 is activated by allergen. However, the true fact needs future study to discover.