A question arises now is, by which TLR2 crosstalks with NLRP3 inflammasome and consequently mediates allergic airway inflammation. Melatonin has been reported to exert important immune-modulating effects in allergic airway diseases (19, 20, 48, 49), and the level of melatonin in saliva or serum of asthma patients were significantly lower than those in healthy controls (21, 50, 51). Particularly, it has been shown that TLR9 signaling regulates endogenous melatonin synthesis in allergic airway inflammation (22). Considering TLR2 and TLR9 are structurally similar, we asked whether TLR2 regulates endogenous melatonin synthesis and thereby modulated NLRP3 inflammasome activity. Indeed, the current study demonstrated that TLR2 protein expression was remarkably increased accompanying with decreased expression of melatonin synthetase ASMT and lower level of melatonin in lung homogenate in WT mice post OVA challenge, while deletion of TLR2 significantly rescued melatonin biosynthesis. Since it have been reported that C57BL/6 mice were pineal melatonin-deficient mice (52, 53) or produce much lower melatonin in their pineal gland (17, 54), suggested an extra-pineal melatonin synthesis might compensate for the pineal deficiency (17). Actually, there are results reporting that several extra-pineal tissues, such as thymus, spleen and skin, in C57BL/6 mice can synthesize melatonin (17, 55), our current study further found that another extra-pineal tissue, i.e., lung synthesized melatonin, and this process maybe modulated by TLR2 signal.