Dataset Information

Protein turnover rate along the gastrointestinal tract is coordinated by the spatial location and the microbiota

ABSTRACT: The gastrointestinal tract is covered by a single layer of epithelial cells that, together with the mucus layers, protect the underlying tissue from bacterial invasion. The epithelium has one of the highest turnover rates in the body, renewing every 4-5 days. Using stable isotope labelling, high-resolution mass spectrometry and computational analysis, we report here a comprehensive dataset of the turnover rate of 3041 and the expression of 5012 intestinal epithelial cell proteins, analyzed under conventional and germ-free conditions across five different segments in mouse intestine. The median protein half-life was shorter in small intestine compared to colon, ranging from 3.5 to 4.2 days. Differences in protein turnover rates along the intestinal tract can be explained by distinct physiological functions and site-specific immune responses between the small and large intestine. Absence of microflora resulted in increased protein half-life by approximately one day.

INSTRUMENT(S): LTQ Orbitrap, Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Colon, Gastrointestinal Mucosa, Small Intestine

DISEASE(S): Disease Free

SUBMITTER: Liisa Arike

LAB HEAD: Liisa Arike

PROVIDER: PXD011457 | Pride | 2020-01-24

REPOSITORIES: Pride

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Publications

Protein Turnover in Epithelial Cells and Mucus along the Gastrointestinal Tract Is Coordinated by the Spatial Location and Microbiota.

Arike Liisa L Seiman Andrus A van der Post Sjoerd S Rodriguez Piñeiro Ana M AM Ermund Anna A Schütte André A Bäckhed Fredrik F Johansson Malin E V MEV Hansson Gunnar C GC

Cell reports 20200128 4

The gastrointestinal tract is covered by a single layer of epithelial cells that, together with the mucus layers, protect the underlying tissue from microbial invasion. The epithelium has one of the highest turnover rates in the body. Using stable isotope labeling, high-resolution mass spectrometry, and computational analysis, we report a comprehensive dataset of the turnover of more than 3,000 and the expression of more than 5,000 intestinal epithelial cell proteins, analyzed under conventional ...[more]

PMID: 31995731

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Project description:Miao2010 - Innate and adaptive immune responses to primary Influenza A Virus infection This model is described in the article: Quantifying the early immune response and adaptive immune response kinetics in mice infected with influenza A virus. Miao H, Hollenbaugh JA, Zand MS, Holden-Wiltse J, Mosmann TR, Perelson AS, Wu H, Topham DJ. J. Virol. 2010 Jul; 84(13): 6687-6698 Abstract: Seasonal and pandemic influenza A virus (IAV) continues to be a public health threat. However, we lack a detailed and quantitative understanding of the immune response kinetics to IAV infection and which biological parameters most strongly influence infection outcomes. To address these issues, we use modeling approaches combined with experimental data to quantitatively investigate the innate and adaptive immune responses to primary IAV infection. Mathematical models were developed to describe the dynamic interactions between target (epithelial) cells, influenza virus, cytotoxic T lymphocytes (CTLs), and virus-specific IgG and IgM. IAV and immune kinetic parameters were estimated by fitting models to a large data set obtained from primary H3N2 IAV infection of 340 mice. Prior to a detectable virus-specific immune response (before day 5), the estimated half-life of infected epithelial cells is approximately 1.2 days, and the half-life of free infectious IAV is approximately 4 h. During the adaptive immune response (after day 5), the average half-life of infected epithelial cells is approximately 0.5 days, and the average half-life of free infectious virus is approximately 1.8 min. During the adaptive phase, model fitting confirms that CD8(+) CTLs are crucial for limiting infected cells, while virus-specific IgM regulates free IAV levels. This may imply that CD4 T cells and class-switched IgG antibodies are more relevant for generating IAV-specific memory and preventing future infection via a more rapid secondary immune response. Also, simulation studies were performed to understand the relative contributions of biological parameters to IAV clearance. This study provides a basis to better understand and predict influenza virus immunity. This model is hosted on BioModels Database and identified by: BIOMD0000000546. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Protein turnover rate along the gastrointestinal tract is coordinated by the spatial location and the microbiota

Publications

Protein Turnover in Epithelial Cells and Mucus along the Gastrointestinal Tract Is Coordinated by the Spatial Location and Microbiota.

Similar Datasets

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