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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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Autores principales: Wang, Xin, Khoshaba, Ramina, Shen, Yi, Cao, Yu, Lin, Minglin, Zhu, Yun, Cao, Zhe, Liao, Duan-Fang, Cao, Deliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907435/
https://www.ncbi.nlm.nih.gov/pubmed/33644071
http://dx.doi.org/10.3389/fcell.2021.632805
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author Wang, Xin
Khoshaba, Ramina
Shen, Yi
Cao, Yu
Lin, Minglin
Zhu, Yun
Cao, Zhe
Liao, Duan-Fang
Cao, Deliang
author_facet Wang, Xin
Khoshaba, Ramina
Shen, Yi
Cao, Yu
Lin, Minglin
Zhu, Yun
Cao, Zhe
Liao, Duan-Fang
Cao, Deliang
author_sort Wang, Xin
collection PubMed
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.
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spelling pubmed-79074352021-02-27 Impaired Barrier Function and Immunity in the Colon of Aldo-Keto Reductase 1B8 Deficient Mice Wang, Xin Khoshaba, Ramina Shen, Yi Cao, Yu Lin, Minglin Zhu, Yun Cao, Zhe Liao, Duan-Fang Cao, Deliang Front Cell Dev Biol Cell and Developmental Biology 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. Frontiers Media S.A. 2021-02-12 /pmc/articles/PMC7907435/ /pubmed/33644071 http://dx.doi.org/10.3389/fcell.2021.632805 Text en Copyright © 2021 Wang, Khoshaba, Shen, Cao, Lin, Zhu, Cao, Liao and Cao. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Wang, Xin
Khoshaba, Ramina
Shen, Yi
Cao, Yu
Lin, Minglin
Zhu, Yun
Cao, Zhe
Liao, Duan-Fang
Cao, Deliang
Impaired Barrier Function and Immunity in the Colon of Aldo-Keto Reductase 1B8 Deficient Mice
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 Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907435/
https://www.ncbi.nlm.nih.gov/pubmed/33644071
http://dx.doi.org/10.3389/fcell.2021.632805
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