Melatonergic Signaling Sustains Food Allergy Through FcεRI Recycling
Youxia Wang,
Xinmei Zhang,
Ifen Hung,
Chunxue Liu,
Wenkai Ren,
Liangpeng Ge,
Hao Wang
Affiliations
Youxia Wang
State Key Laboratory of Livestock and Poultry Breeding, Guangdong Laboratory of Lingnan Modern Agriculture, College of Animal Science,
South China Agricultural University, Guangzhou, China.
Xinmei Zhang
State Key Laboratory of Livestock and Poultry Breeding, Guangdong Laboratory of Lingnan Modern Agriculture, College of Animal Science,
South China Agricultural University, Guangzhou, China.
Ifen Hung
Anyou Biotechnology Group Co. Ltd., Taicang, China.
Chunxue Liu
Anyou Biotechnology Group Co. Ltd., Taicang, China.
Wenkai Ren
State Key Laboratory of Livestock and Poultry Breeding, Guangdong Laboratory of Lingnan Modern Agriculture, College of Animal Science,
South China Agricultural University, Guangzhou, China.
Liangpeng Ge
National Center of Technology Innovation for Pigs; Chongqing Academy of Animal Sciences; Key Laboratory of Pig Industry Science, Ministry of Agriculture, Chongqing, China.
Hao Wang
State Key Laboratory of Livestock and Poultry Breeding, Guangdong Laboratory of Lingnan Modern Agriculture, College of Animal Science,
South China Agricultural University, Guangzhou, China.
The prevalence of food allergies is increasing dramatically and causing serious public health concerns. Notably, melatonin metabolism imbalance in patients with food allergies; however, the role of melatonin in food allergies remains unclear. Here, we demonstrated that melatonin suppresses food allergy responses and reprograms the gut microbiota of food-allergic mice, while melatonin aggravates food allergy during gut microbiota depletion. Mechanistically, melatonin boosts the degranulation of mast cells by up-regulating the expression of membrane high-affinity immunoglobulin E (IgE) receptor (FcεRI). Melatonin increases the mRNA expression of Rabenosyn-5 (a component of factors for endosome recycling and Rab interactions) through melatonin receptor 2 (MT2)–extracellular signal-regulated kinase (ERK) signaling, thereby driving the recycling of FcεRI and elevating the abundance of membrane FcεRI. Likewise, the inhibition of MT2 attenuates melatonin-induced food allergy in mice with gut microbiota depletion. Collectively, our finding provides insights into the pathogenesis of food allergies and provides a potential therapeutic target for the prevention and treatment of food allergies.
