Melatonergic signaling sustains food allergy through FceRI recycling

https://spj.science.org/doi/pdf/10.34133/research.0418

https://spj.science.org on June 17, 2024

Youxia Wang, Xinmei Zhang, Ifen Hung, Chunxue Liu, Wenkai Ren, Liangpeng Ge and Hao Wang

Abstract

The prevalence of food allergies is increasing dramatically and causing serious public health concerns. Notably, melatonin metabolism imbalance in the progression of 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.

Key words: Melatonin; food allergy; mast cells; FcεRI; endocytic recycling

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