Modeling And Analysis Of The Regulation Of CD4+ Th17 Cell Differentiation By Segmented Filamentous Bacteria

CD4+ T cells(Th17 cells)are considered to be a unique lineage of CD4+ T helper(Th)cells that play important roles in host defense,tissue inflammation,and autoimmunity.The identification of Th17 cells breaks the notion of the Th1/Th2 paradigm previously held in infection and autoimmunity.Th17 cells play a key role in the functioning of a healthy immune system and protect the host from bacterial and fungal infections,especially on mucosal surfaces,but are also thought to have a pathogenic role in autoimmunity,asthma,cancer,and allergic reactions.Segmented filamentous bacteria are specific inducers that promote the differentiation of CD4+ Th17 cells,and at the same time,Th17 induces epithelial cells to produce antimicrobial peptides,which can limit the adhesion and colonization of SFB and maintain local immune balance.The symbiotic relationship between the gut microbiota and cells of the host immune system promotes homeostasis,ensuring that the microbial community and balance are maintained.Dysbiosis caused by diet,age,antibiotics,etc.can alter the abundance of SFB.Studies have shown that SFB abundance changes with age,first increasing and then decreasing at weaning,but SFB abundance remains low in adulthood;rich diets can control SFB abundance;antibiotics can destroy gut bacteria to alter flora abundance.In the existing research,the mechanism of Th17 differentiation is relatively complete,but the quantitative research on the related model of SFB for Th17 cell differentiation is not sufficient.Here,we develop a multiscale,multicellular model to demonstrate cellular and protein network mechanisms to characterize how SFB specifically stimulates Th17 immunity and to highlight the important role of flagellin as an SFB antigen.In the existing model,the effect on Th17 differentiation and the killing efficiency of antimicrobial peptides was explored by changing the abundance of SFB in the context of dysbiosis,and the results were divided into three aspects: SFB promoted Th17 differentiation,induced The expression of IL-17 A and IL-22 was increased,resulting in the production of antimicrobial peptides to limit the proliferation of SFB;within a certain range,the higher the abundance of SFB,the greater the number of Th17 could be induced,but the decrease of IL-17 A and IL at the same time The expression of-22,which in turn led to a decrease in the ability of antimicrobial peptides to kill bacteria,aggravated the dysbiosis;compared with the control group,after adding antibiotics,SFB was inhibited,the secretion of flagellin was lower,and DCs matured later,the number peak was lower,Th17 cells appeared later,and the total concentration of IL-17 A and IL-22 increased slowly in the early stage,resulting in lower expression of antimicrobial peptides.This study is beneficial to study the mechanism by which Th17 cells play a pathogenic or protective role in infection and inflammatory diseases in an antigen-dependent manner.