Chronic Restraint Stress-induced Intestinal Mucosal Immune Dysfunction

Objective:To explore the mechanism of intestinal mucosal immune imbalance caused by chronic restraint stress(CRS),clarify the intestinal local mucosal immune pattern under depression state,and provide new insights for the prevention and treatment of depression based on the brain-gut axis theory.Methods:(1)Induced depression-like behavior in mice by the CRS model.(2)The levels of intestinal lysozyme and antimicrobial peptides were detected by immunofluorescence staining and q PCR.(3)The proportion of the intestinal group 3 innate lymphoid cells(ILC3)and intraepithelial lymphocytes(IEL)was detected by flow cytometry.(4)The levels of CTB-specific immunoglobulins(Igs)in serum and intestine were detected by ELISA after mice were orally immunized with cholera toxin B(CTB).(5)16S r RNA sequencing technology was used to analyze the alteration of intestinal microbiota composition and function.Results:(1)Compared with wildtype mice,CRS mice showed significantly shortened villus length of duodenum and jejunum,increased crypt depth,and decreased ratio of villus length to crypt depth.(2)The expression of lysozyme and the secretion of antimicrobial peptides Defa3and Defa4 were significantly decreased in Paneth cells of the stressed mice.(3)Although the proportion of IEL in small intestine did not change significantly,the proportion and absolute number of NKp46~+ILC3 decreased significantly.(4)The level of intestinal CTB-specific Ig A production was significantly decreased,and the relative abundance of the intestinal flora relating to Ig A function-associated lipopolysaccharide biosynthesis was also significantly reduced in the stressed mice.Conclusion:CRS affects intestinal innate immune homeostasis,destroying the intestinal humoral immunity and dynamic balance of intestinal flora.