The Mechanism Of AKT Pathway Mediating Exogenous Cadaverine To Alleviate Food Allergy

Cadaverine is a kind of natural amine with various biological activities.It is widely found in the daily diet of fermented food and aquatic products.The role of cadaverine bioactivity in humans covers a wide range of functions,including influencing cell apoptosis,division,differentiation,proliferation,DNA and protein synthesis,gene expression signal transduction,and homeostasis.At present,there is no paper has reported that cells and tissues produce cadaverine,so the source of cadaverine in the body mainly depends on exogenous uptake.In recent years,biogenic amines have been found to interact with the immune system,polyamines regulate the expression of immune-related genes,and polyamine metabolism affects T-cell differentiation.But there has been a lack of studies on cadaverine interacting with the immune system,and on cadaverine interacting with food allergies.Based on this,this paper is devoted to studying the immune regulatory effect of cadaverine on food-allergic mice and immune cells,as well as the discovery of cadaverine target cells and target signals.The main research contents are as follows:(1)The OVA food allergy mouse model was established to study the immune mechanism of trace cadaverine to OVA food allergy mice.The results showed that trace cadaverine significantly alleviated food allergy symptoms in Balb/c mice,regulated Th1/Th2 differentiation to achieve dynamic balance,restored Th2 polarization caused by allergy,and up-regulated the proportion of Treg cells to promote immune tolerance.Cadaverine regulates the expression of T cells and inflammation-related genes in the direction of alleviating allergies.In addition,it significantly activated the DC2.4 cells AKT pathway and enriched the intestinal microflora of allergic mice.(2)Through in vitro experiments,explore the mechanism of trace cadaverine alleviating the sensitizing activity of immune cells(spleen cells,PBMC,DC2.4,CMT93).The results verified that cadaverine up-regulated the secretion of Th1 and Treg-related cytokines(IFN-γ,IL-10).The gene expressions of Th1,Treg-related cytokines and transcription factors(IFN-γ,T-bet,Foxp3)were up-regulated,and Th2 related cytokines and transcription factors(IL-4,GATA3)were down-regulated,and the gene expressions of pro-inflammatory factors(IL-33,TSLP,OX40L)were downregulated.PBMC transcriptome revealed that cadaverine significantly up-regulated antigen processing and presentation,immune response and other functions.DC2.4transcriptome revealed that cadaverine significantly up-regulated PI3K-AKT pathway.(3)DC cells were identified as the target cells of trace cadaverine.Through singlecell model(DC2.4)and co-culture cell model(DC2.4+ spleen cells),using the AKT inhibitor,we verified that the AKT pathway in DC2.4 was activated by trace cadaverine.We further explored trace cadaverine through activation of AKT pathway regulate the gene expression of DC2.4,and further regulation of T cell gene expression and Th1 differentiation.A single cell model(DC2.4)was used to verify that trace cadaverine activates the AKT pathway of DC2.4 and regulates the gene expression level of DC2.4;Secondly,by using a co cultured cell model(DC2.4+spleen cells),trace cadaverine were investigated to regulate DC2.4 gene expression by activating the AKT pathway,and further regulate T cell gene expression and Th1 differentiation;To determine the target cells(DC)and target signaling pathways(AKT signaling pathway)for trace cadaverine to alleviate food allergies...