Inflammatory bowel disease (IBD) is a disorder of immune and microbial dysregulation, induced by environmental factors in a genetically predisposed individual. Studies on IBD-associated genes have demonstrated that Paneth cells (PC) are central to the pathogenesis of IBD, especially in the development of Crohn′s disease (CD). The morphology, quantity and function of PC are easily affected by susceptible genes. In the intestine, PC participate in the formation of stem cell niche and secrete antimicrobial particles, which plays a vital role in regulating intestinal microbiota and maintaining intestinal mucosal homeostasis. Meanwhile, the proliferation and maturation of PC are also dependent on the symbiotic microbiota in the intestine. This review focuses on the interaction of susceptible genes, PC and intestinal microbiota, as well as their influence on the occurrence and development of IBD.

Inflammatory bowel disease (IBD) is a disorder of immune and microbial dysregulation, induced by environmental factors in a genetically predisposed individual. Studies on IBD-associated genes have demonstrated that Paneth cells (PC) are central to the pathogenesis of IBD, especially in the development of Crohn′s disease (CD). The morphology, quantity and function of PC are easily affected by susceptible genes. In the intestine, PC participate in the formation of stem cell niche and secrete antimicrobial particles, which plays a vital role in regulating intestinal microbiota and maintaining intestinal mucosal homeostasis. Meanwhile, the proliferation and maturation of PC are also dependent on the symbiotic microbiota in the intestine. This review focuses on the interaction of susceptible genes, PC and intestinal microbiota, as well as their influence on the occurrence and development of IBD.

Objective:To investigate the influence of death receptor 3 ( Dr3) gene deficiency on the intestinal mucosal inflammation in different mice colitis models, and explore the relationship of Dr3 gene deficiency and intestinal mucosal permeability. Methods:Nine female Dr3 gene deficiency ( Dr3-/-) mice and 9 wild type (WT) mice were collected and set as Dr3-/--DSS group and WT-DSS group. The mice of 2 groups received 2.5% dextran sodium sulfate (DSS) for 5 days and sterile water for 2 days as a cycle and 4 cycles were manipulated to construct a chronic colitis model of mice. The male WT and Dr3-/- mice were collected as donor mice and initial T lymphocytes from two types of donor mice were sorted respectively by immunomagnetic separation and flow cytometry. A enteritis model of mice induced by T cells adoptive transfer was constructed on the recipient mice including Rag1-/- (WT transfer group) and Dr3-/-Rag1-/- ( Dr3-/- transfer group) mice by the peritoneal injection of T lymphocytes from WT and Dr3-/- mice respectively. The body mass, stool property and occult blood of mice were observed, and the disease activity index (DAI) was calculated. The degree of intestinal mucosal injury and inflammatory cell infiltration in mice were observed under microscope, and the histological score of enteritis was calculated. The intestinal mucosal permeability of mice was detected by fluorescein isothiocyanate (FITC) -dextran serum fluorescence method. The differences of DAI score, histological score and FITC-dextran content between the two groups were compared. Results:The DAI scores of mice in Dr3-/--DSS group were significantly higher than those in WT-DSS group on the 12th, 19th and 26th day after establishing the model (all P<0.05) . The rectal histological score of WT-DSS group 4 weeks after establishing the model was significantly higher than that of cecum and colon (10.130 ± 1.540 vs. 3.667 ± 0.236 and 7.222 ± 1.199, all P<0.05) , suggesting that the degree of rectal inflammation in WT-DSS group was the most serious. The histological score of colon in Dr3-/--DSS group was significantly higher than that of cecum and rectum (11.330 ± 1.167 vs. 7.556 ± 1.519 and 9.500 ± 0.824, all P<0.05) , suggesting that the degree of colonic inflammation in Dr3-/--DSS group was the most serious. The histological scores of cecum and colon in Dr3-/--DSS group were significantly higher than those of WT-DSS group (cecum: 7.556 ± 1.519 vs. 3.667 ± 0.236, P = 0.022; colon: 11.330 ± 1.167 vs. 7.222 ± 1.199, P = 0.026) , but there was no significant difference in rectal histological score between the two groups ( P>0.05) , suggesting that Dr3 gene deficiency aggravated the inflammation of cecum and colon. The rectal histological score of WT transfer group 6 weeks after establishing the model was significantly higher than that of duodenum, jejunum, terminal ileum, cecum and middle colon (all P<0.05) , suggesting that the degree of rectal inflammation in WT transfer group was the most serious. The histological score of cecum in Dr3-/- transfer group was significantly higher than that of duodenum, jejunum, terminal ileum, middle colon and rectum (all P<0.05) , suggesting that the degree of cecal inflammation in WT transfer group was the most serious. Compared with WT transfer group, the scores of small intestine including duodenum, jejunum and terminal ileum in Dr3-/- transfer group were significantly higher (17.667 ± 0.943 vs. 14.667 ± 1.167, P<0.05) , and the infiltration of inflammatory cells in small intestine was more obvious (duodenum: 4.000 ± 0.289 vs. 3.222 ± 0.401, P = 0.135; jejunum: 4.000 ± 0.236 vs. 3.111 ± 0.309, P<0.05; ileum: 4.889 ± 0.309 vs. 3.889 ± 0.261, P<0.05) . It was suggested that Dr3 gene deficiency aggravated intestinal inflammation. The content of FITC-dextran in eye venous blood of Dr3-/- mice was significantly higher than that of WT mice (656.0 ± 60.9 vs. 403.8 ± 54.8, P<0.05) , the content of FITC-dextran in Dr3-/--DSS group was significantly higher than that of WT-DSS group (1176.4 ± 109.5 vs. 545.7 ± 97.8, P<0.05) , the content of FITC-dextran in Dr3-/-transfer group was significantly higher than that of WT transfer group (1270.5 ± 112.2 vs. 711.0 ± 71.5, P<0.05) , and the content of FITC-dextran in Dr3-/-Rag1-/- mice was significantly higher than that of Rag1-/- mice (714.5 ± 62.9 vs. 501.8 ± 59.8, P<0.05) , suggesting that the intestinal mucosal permeability of Dr3 gene deficient mice was higher. Conclusion:Dr3 gene deficiency in mice increases intestinal mucosal permeability, destroys intestinal mucosal barrier function, and aggravates intestinal proximal inflammation in experimental colitis, suggesting that Dr3 gene may play the protective role in intestinal inflammation by regulating intestinal mucosal permeability.

Objective:To investigate the influence of death receptor 3 ( Dr3) gene deficiency on the intestinal mucosal inflammation in different mice colitis models, and explore the relationship of Dr3 gene deficiency and intestinal mucosal permeability. Methods:Nine female Dr3 gene deficiency ( Dr3-/-) mice and 9 wild type (WT) mice were collected and set as Dr3-/--DSS group and WT-DSS group. The mice of 2 groups received 2.5% dextran sodium sulfate (DSS) for 5 days and sterile water for 2 days as a cycle and 4 cycles were manipulated to construct a chronic colitis model of mice. The male WT and Dr3-/- mice were collected as donor mice and initial T lymphocytes from two types of donor mice were sorted respectively by immunomagnetic separation and flow cytometry. A enteritis model of mice induced by T cells adoptive transfer was constructed on the recipient mice including Rag1-/- (WT transfer group) and Dr3-/-Rag1-/- ( Dr3-/- transfer group) mice by the peritoneal injection of T lymphocytes from WT and Dr3-/- mice respectively. The body mass, stool property and occult blood of mice were observed, and the disease activity index (DAI) was calculated. The degree of intestinal mucosal injury and inflammatory cell infiltration in mice were observed under microscope, and the histological score of enteritis was calculated. The intestinal mucosal permeability of mice was detected by fluorescein isothiocyanate (FITC) -dextran serum fluorescence method. The differences of DAI score, histological score and FITC-dextran content between the two groups were compared. Results:The DAI scores of mice in Dr3-/--DSS group were significantly higher than those in WT-DSS group on the 12th, 19th and 26th day after establishing the model (all P<0.05) . The rectal histological score of WT-DSS group 4 weeks after establishing the model was significantly higher than that of cecum and colon (10.130 ± 1.540 vs. 3.667 ± 0.236 and 7.222 ± 1.199, all P<0.05) , suggesting that the degree of rectal inflammation in WT-DSS group was the most serious. The histological score of colon in Dr3-/--DSS group was significantly higher than that of cecum and rectum (11.330 ± 1.167 vs. 7.556 ± 1.519 and 9.500 ± 0.824, all P<0.05) , suggesting that the degree of colonic inflammation in Dr3-/--DSS group was the most serious. The histological scores of cecum and colon in Dr3-/--DSS group were significantly higher than those of WT-DSS group (cecum: 7.556 ± 1.519 vs. 3.667 ± 0.236, P = 0.022; colon: 11.330 ± 1.167 vs. 7.222 ± 1.199, P = 0.026) , but there was no significant difference in rectal histological score between the two groups ( P>0.05) , suggesting that Dr3 gene deficiency aggravated the inflammation of cecum and colon. The rectal histological score of WT transfer group 6 weeks after establishing the model was significantly higher than that of duodenum, jejunum, terminal ileum, cecum and middle colon (all P<0.05) , suggesting that the degree of rectal inflammation in WT transfer group was the most serious. The histological score of cecum in Dr3-/- transfer group was significantly higher than that of duodenum, jejunum, terminal ileum, middle colon and rectum (all P<0.05) , suggesting that the degree of cecal inflammation in WT transfer group was the most serious. Compared with WT transfer group, the scores of small intestine including duodenum, jejunum and terminal ileum in Dr3-/- transfer group were significantly higher (17.667 ± 0.943 vs. 14.667 ± 1.167, P<0.05) , and the infiltration of inflammatory cells in small intestine was more obvious (duodenum: 4.000 ± 0.289 vs. 3.222 ± 0.401, P = 0.135; jejunum: 4.000 ± 0.236 vs. 3.111 ± 0.309, P<0.05; ileum: 4.889 ± 0.309 vs. 3.889 ± 0.261, P<0.05) . It was suggested that Dr3 gene deficiency aggravated intestinal inflammation. The content of FITC-dextran in eye venous blood of Dr3-/- mice was significantly higher than that of WT mice (656.0 ± 60.9 vs. 403.8 ± 54.8, P<0.05) , the content of FITC-dextran in Dr3-/--DSS group was significantly higher than that of WT-DSS group (1176.4 ± 109.5 vs. 545.7 ± 97.8, P<0.05) , the content of FITC-dextran in Dr3-/-transfer group was significantly higher than that of WT transfer group (1270.5 ± 112.2 vs. 711.0 ± 71.5, P<0.05) , and the content of FITC-dextran in Dr3-/-Rag1-/- mice was significantly higher than that of Rag1-/- mice (714.5 ± 62.9 vs. 501.8 ± 59.8, P<0.05) , suggesting that the intestinal mucosal permeability of Dr3 gene deficient mice was higher. Conclusion:Dr3 gene deficiency in mice increases intestinal mucosal permeability, destroys intestinal mucosal barrier function, and aggravates intestinal proximal inflammation in experimental colitis, suggesting that Dr3 gene may play the protective role in intestinal inflammation by regulating intestinal mucosal permeability.