Impaired Barrier Function and Immunity in the Colon of Aldo-Keto Reductase 1B8 Deficient Mice
Aldo-keto reductase 1B10 (AKR1B10) is downregulated in human ulcerative colitis (UC) and colorectal cancer, being a potential pathogenic factor of these diseases. Aldo-keto reductase 1B8 (AKR1B8) is the ortholog in mice of human AKR1B10. Targeted AKR1B8 deficiency disrupts homeostasis of epithelial...
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.632805/full |
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| author | Xin Wang Ramina Khoshaba Ramina Khoshaba Yi Shen Yu Cao Minglin Lin Yun Zhu Zhe Cao Duan-Fang Liao Deliang Cao |
| author_facet | Xin Wang Ramina Khoshaba Ramina Khoshaba Yi Shen Yu Cao Minglin Lin Yun Zhu Zhe Cao Duan-Fang Liao Deliang Cao |
| author_sort | Xin Wang |
| collection | DOAJ |
| description | Aldo-keto reductase 1B10 (AKR1B10) is downregulated in human ulcerative colitis (UC) and colorectal cancer, being a potential pathogenic factor of these diseases. Aldo-keto reductase 1B8 (AKR1B8) is the ortholog in mice of human AKR1B10. Targeted AKR1B8 deficiency disrupts homeostasis of epithelial self-renewal and leads to susceptibility to colitis and carcinogenesis. In this study, we found that in AKR1B8 deficient mice, Muc2 expression in colon was diminished, and permeability of colonic epithelium increased. Within 24 h, orally administered FITC-dextran penetrated into mesenteric lymph nodes (MLN) and liver in AKR1B8 deficient mice, but not in wild type controls. In the colon of AKR1B8 deficient mice, neutrophils and mast cells were markedly infiltrated, γδT cells were numerically and functionally impaired, and dendritic cell development was altered. Furthermore, Th1, Th2, and Th17 cells decreased, but Treg and CD8T cells increased in the colon and MLN of AKR1B8 deficient mice. In colonic epithelial cells of AKR1B8 deficient mice, p-AKT (T308 and S473), p-ERK1/2, p-IKBα, p-p65 (S536), and IKKα expression decreased, accompanied with downregulation of IL18 and CCL20 and upregulation of IL1β and CCL8. These data suggest AKR1B8 deficiency leads to abnormalities of intestinal epithelial barrier and immunity in colon. |
| first_indexed | 2024-12-21T14:12:46Z |
| format | Article |
| id | doaj.art-b12cdaf4990e4ffbbe2106a33b6a141b |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-21T14:12:46Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-b12cdaf4990e4ffbbe2106a33b6a141b2022-12-21T19:01:00ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-02-01910.3389/fcell.2021.632805632805Impaired Barrier Function and Immunity in the Colon of Aldo-Keto Reductase 1B8 Deficient MiceXin Wang0Ramina Khoshaba1Ramina Khoshaba2Yi Shen3Yu Cao4Minglin Lin5Yun Zhu6Zhe Cao7Duan-Fang Liao8Deliang Cao9Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL, United StatesDepartment of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL, United StatesDepartment of Biotechnology, College of Science, University of Baghdad, Baghdad, IraqDepartment of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL, United StatesDepartment of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL, United StatesDepartment of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL, United StatesDepartment of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL, United StatesDepartment of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL, United StatesState Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), Division of Stem Cell Regulation and Application, Hunan University of Chinese Medicine, Changsha, ChinaDepartment of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL, United StatesAldo-keto reductase 1B10 (AKR1B10) is downregulated in human ulcerative colitis (UC) and colorectal cancer, being a potential pathogenic factor of these diseases. Aldo-keto reductase 1B8 (AKR1B8) is the ortholog in mice of human AKR1B10. Targeted AKR1B8 deficiency disrupts homeostasis of epithelial self-renewal and leads to susceptibility to colitis and carcinogenesis. In this study, we found that in AKR1B8 deficient mice, Muc2 expression in colon was diminished, and permeability of colonic epithelium increased. Within 24 h, orally administered FITC-dextran penetrated into mesenteric lymph nodes (MLN) and liver in AKR1B8 deficient mice, but not in wild type controls. In the colon of AKR1B8 deficient mice, neutrophils and mast cells were markedly infiltrated, γδT cells were numerically and functionally impaired, and dendritic cell development was altered. Furthermore, Th1, Th2, and Th17 cells decreased, but Treg and CD8T cells increased in the colon and MLN of AKR1B8 deficient mice. In colonic epithelial cells of AKR1B8 deficient mice, p-AKT (T308 and S473), p-ERK1/2, p-IKBα, p-p65 (S536), and IKKα expression decreased, accompanied with downregulation of IL18 and CCL20 and upregulation of IL1β and CCL8. These data suggest AKR1B8 deficiency leads to abnormalities of intestinal epithelial barrier and immunity in colon.https://www.frontiersin.org/articles/10.3389/fcell.2021.632805/fullaldo-keto reductase 1B8intestinal epithelial cellsintestinal immunitycytokinesAKT and ERK signaling pathways |
| spellingShingle | Xin Wang Ramina Khoshaba Ramina Khoshaba Yi Shen Yu Cao Minglin Lin Yun Zhu Zhe Cao Duan-Fang Liao Deliang Cao Impaired Barrier Function and Immunity in the Colon of Aldo-Keto Reductase 1B8 Deficient Mice Frontiers in Cell and Developmental Biology aldo-keto reductase 1B8 intestinal epithelial cells intestinal immunity cytokines AKT and ERK signaling pathways |
| title | Impaired Barrier Function and Immunity in the Colon of Aldo-Keto Reductase 1B8 Deficient Mice |
| title_full | Impaired Barrier Function and Immunity in the Colon of Aldo-Keto Reductase 1B8 Deficient Mice |
| title_fullStr | Impaired Barrier Function and Immunity in the Colon of Aldo-Keto Reductase 1B8 Deficient Mice |
| title_full_unstemmed | Impaired Barrier Function and Immunity in the Colon of Aldo-Keto Reductase 1B8 Deficient Mice |
| title_short | Impaired Barrier Function and Immunity in the Colon of Aldo-Keto Reductase 1B8 Deficient Mice |
| title_sort | impaired barrier function and immunity in the colon of aldo keto reductase 1b8 deficient mice |
| topic | aldo-keto reductase 1B8 intestinal epithelial cells intestinal immunity cytokines AKT and ERK signaling pathways |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.632805/full |
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