Analysis Of The Association Between Histidine And Food Allergy And Its Regulatory Mechanism

Over the past few decades,the prevalence of allergic diseases has grown rapidly worldwide,and allergic diseases have become the sixth largest disease in the world,with food allergies accounting for a large proportion.Food allergy is a pathological response of the immune system triggered by ingested food protein antigens.Among them,Ig E-mediated food allergy is the most characteristic type of food allergy with a clear mechanism.The level of amino acids in different groups of people is different,and amino acid homeostasis plays an important role in the normal operation of the body’s innate and adaptive immune systems.A variety of amino acids are involved in the maintenance of cell function of cells related to allergic reactions,including dendritic cells,basophils,mast cells,lymphocytes,etc.,thereby regulating the occurrence of food allergy.In view of this,based on the previous two allergic population trials,this study further explored the association between histidine and allergic diseases and found that there was a differential expression of histidine in allergic people,and the intestinal histidine level of people with allergic diseases was significantly higher than that in the general population.Through the correlation analysis of histidine differential expression and allergic population questionnaires,cytokines(IL-4,IL-5,etc.),immunoglobulins(Ig E,Ig G1,etc.),blood routine(monocytes,eosinophils,basophils,etc.),the role of histidine in allergic diseases,including food allergy,was explored,and it was found that high levels of histidine were significantly positively correlated with the occurrence of allergic diseases,total serum Ig E and Ig G1 levels.It has been shown that high levels of histidine have a promoting effect on allergic diseases.Subsequently,high-level histidine intervention was used in vitro single-cell models(mouse intestinal epithelial cells,dendritic cells,spleen cells)and food antigen-sensitized intestinal models(mouse intestinal epithelial cells,spleen cells,CD4~+T cells)to further explore the specific regulatory effect of high levels of histidine on allergy-associated immune cells.It was found that histidine can regulate allergy-related immune cells in multiple aspects,and high-level histidine intervention promoted the expression of TSLP in mouse intestinal epithelial cells,OX40L,IL-16,IL-6 and other pro-inflammatory genes in dendritic cells,and promoted the development of intestinal epithelial cells and dendritic cells in the direction of pro-inflammation.At the same time,high levels of histidine downregulated the expression of transcription factor T-bet and cytokine IFN-γgenes in Th1 cells,reducing the activity of Th1 cells.Increase the expression of Th2 cell transcription factor GATA-3,promote Th2 cell differentiation,enhance Th2 cell activity,and make the balance of Th1/Th2 cells in the body biased towards Th2 cells.High levels of histidine further upregulate Ig E gene expression in B cells,promote Ig E secretion by B cells,and increase the risk of food allergy.Finally,using dendritic cells as the main target cells,the effect of histidine on dendritic cells was explored by flow cytometry.The study found that histidine intervention significantly enhanced the phagocytic ability of dendritic cell antigens.Transcriptome analysis showed that after high-level histidine intervention,the expression of p65 and p50 genes related to the NF-κB signaling pathway in dendritic cells was significantly upregulated.In western blotting and immunofluorescence analysis,after histidine intervention,the level of IκBαphosphorylation of dendritic cells increased,and nuclear translocation of NF-κB p65 protein occurred,indicating that the NF-κB signaling pathway was activated.The addition of NF-κB signaling pathway inhibitor BAY 11-7085significantly inhibited the rise of NF-κB signaling pathway-related gene p50 and the upregulation of pro-inflammatory factors OX40L and IL-6 caused by high levels of histidine.These results showed that high levels of histidine regulate dendritic cell immune function through the NF-κB signaling pathway,promote dendritic cells to secrete pro-inflammatory cytokines,which in turn affects the shift of T cell balance to Th2 type,and ultimately affects the secretion of Ig E of B cells and induce the occurrence of food allergy.