L-Citrulline inhibits Th2 cell activation via PLAC8 mediated autophagy and L-Citrulline depletion to alleviate pediatric asthma.

Abstract

Asthma is a common childhood chronic respiratory disease characterized by chronic airway inflammation.CD4Th2 cells drive eosinophil-mediated airway inflammation, which plays a pathogenic role in asthma. L-Citrulline(L-Cit) is a naturally occurring non-essential amino acid and is involved in several physiological roles. The objective of this study is to investigate whether L-Cit would alleviate Ovalbumin (OVA)-induced asthma symptoms and explore the underlying mechanisms and activated Th2 cells on apoptosis and EMT in airway epithelial cells. The levels of serum metabolites in asthmatic children and normal volunteers were measured using mass spectrometry. The proportion of Th2 cells in peripheral blood, as well as levels of IgE, PLAC8 and Th2-related cytokines were assessed by flow cytometry and ELISA assay respectively. Administration of lentivirus via vein injection was used in OVA-induced allergy model in BALB/C mice, then gavaged with different dose of L-Cit for 2 weeks as well as intraperitoneally injected PARA and 3-MA. The effect of L-Cit and PLAC8 on Th2 activation, enzymes involved in amino acid metabolism and autophagy were detected using naive CD4T cells isolated from the spleen.We found that L-Cit treatment significantly alleviates OVA induced asthma symptoms, oxidative stress and autophagy. Further, Our study revealed that L-Cit inhibited, NO, ROS and alleviated asthma symptoms through placenta specific 8(PLAC8) mediated autophagy and reprograms of L-Cit metabolism in Th2 cells. In conclusion, we propose that L-Cit represents a potential therapeutic candidate for young patients suffering from chronic asthma.