Summary of Study ST001089

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000728. The data can be accessed directly via it's Project DOI: 10.21228/M8KD6K This work is supported by NIH grant, U2C- DK119886.

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Study IDST001089
Study TitleHost NLRP6 exacerbates graft-versus-host disease independent of microbial diversity
Study SummaryHost NLRP6 regulates innate immune responses and gastrointestinal (GI) homeostasis. It plays a protective role in pathogenic processes such as intestinal colitis and tumorigenesis in a microbiome dependent manner. Host innate immunity and changes in microbial diversity also play a role in the severity of allo-immune-mediated gastrointestinal pathogenic process, namely graft-versus-host disease (GVHD), the principal toxicity after allogeneic bone marrow transplantation (allo-BMT). Herein, we examined the role of NLRP6 in multiple murine models of allo-BMT. In contrast to its role in intestinal colitis, host NLRP6 aggravated GI GVHD. NLRP6-deficient animals showed improved intestinal barrier function, increased levels of tissue repair associated proteins and preserved Goblet and Paneth cell numbers in the GI tract after allo-BMT. The impact of host NLRP6 deficiency in mitigating GVHD was observed regardless of co-housing, antibiotic treatment, or colonizing littermate germ free wild type (WT) and NLRP6 deficient hosts with fecal microbial transplantation from SPF WT and Nlrp6-/- animals. Chimera studies were performed to assess the role of NLRP6 expression on host hematopoietic and non-hematopoietic cells. The allogeneic [B6Ly5.2→Nlrp6-/-] animals demonstrated significantly improved survival compared to the allogeneic [B6Ly5.2→B6] animals, demonstrating that the absence of NLRP6 in host non-hematopoietic cells is crucial for the protection against GVHD, but did not alter the therapeutic graft-versus-tumor effects after BMT. Our results unveil a novel role for NLRP6 and demonstrate a pathogenic role in GVHD that is independent of variations in its intestinal microbiome in contrast to its well-appreciated microbiome-dependent protective role in intestinal colitis and tumorigenesis.
Institute
University of Michigan
Last NameMathew
First NameAnna
Address5112 Brehm Tower
Emailamat@umich.edu
Phone7342328228
Submit Date2018-11-05
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2019-10-11
Release Version1
Anna Mathew Anna Mathew
https://dx.doi.org/10.21228/M8KD6K
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR000728
Project DOI:doi: 10.21228/M8KD6K
Project Title:Host NLRP6 exacerbates graft-versus-host disease independent of microbial diversity
Project Summary:Host NLRP6 regulates innate immune responses and gastrointestinal (GI) homeostasis. It plays a protective role in pathogenic processes such as intestinal colitis and tumorigenesis in a microbiome dependent manner. Host innate immunity and changes in microbial diversity also play a role in the severity of allo-immune-mediated gastrointestinal pathogenic process, namely graft-versus-host disease (GVHD), the principal toxicity after allogeneic bone marrow transplantation (allo-BMT). Herein, we examined the role of NLRP6 in multiple murine models of allo-BMT. In contrast to its role in intestinal colitis, host NLRP6 aggravated GI GVHD. NLRP6-deficient animals showed improved intestinal barrier function, increased levels of tissue repair associated proteins and preserved Goblet and Paneth cell numbers in the GI tract after allo-BMT. The impact of host NLRP6 deficiency in mitigating GVHD was observed regardless of co-housing, antibiotic treatment, or colonizing littermate germ free wild type (WT) and NLRP6 deficient hosts with fecal microbial transplantation from SPF WT and Nlrp6-/- animals. Chimera studies were performed to assess the role of NLRP6 expression on host hematopoietic and non-hematopoietic cells. The allogeneic [B6Ly5.2→Nlrp6-/-] animals demonstrated significantly improved survival compared to the allogeneic [B6Ly5.2→B6] animals, demonstrating that the absence of NLRP6 in host non-hematopoietic cells is crucial for the protection against GVHD, but did not alter the therapeutic graft-versus-tumor effects after BMT. Our results unveil a novel role for NLRP6 and demonstrate a pathogenic role in GVHD that is independent of variations in its intestinal microbiome in contrast to its well-appreciated microbiome-dependent protective role in intestinal colitis and tumorigenesis.
Institute:University of Michigan
Last Name:Mathew
First Name:Anna
Address:5112 Brehm Tower
Email:amat@umich.edu
Phone:7342328228

Subject:

Subject ID:SU001133
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:B6Ly5.2
Species Group:Mammals

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id BMT Type Mice type Site
SA07356611Allogenic NLRP6KO Large Intestine lumen
SA07356712Allogenic NLRP6KO Large Intestine lumen
SA0735689Allogenic NLRP6KO Large Intestine lumen
SA07356910Allogenic NLRP6KO Large Intestine lumen
SA07357025Allogenic NLRP6KO Small Intestine lumen
SA07357127Allogenic NLRP6KO Small Intestine lumen
SA07357228Allogenic NLRP6KO Small Intestine lumen
SA07357326Allogenic NLRP6KO Small Intestine lumen
SA07357415Allogenic WT Large Intestine lumen
SA07357516Allogenic WT Large Intestine lumen
SA07357614Allogenic WT Large Intestine lumen
SA07357713Allogenic WT Large Intestine lumen
SA07357831Allogenic WT Small Intestine lumen
SA07357929Allogenic WT Small Intestine lumen
SA07358030Allogenic WT Small Intestine lumen
SA07358132Allogenic WT Small Intestine lumen
SA0735821Naïve NLRP6KO Large Intestine lumen
SA0735832Naïve NLRP6KO Large Intestine lumen
SA0735843Naïve NLRP6KO Large Intestine lumen
SA07358517Naïve NLRP6KO Small Intestine lumen
SA07358618Naïve NLRP6KO Small Intestine lumen
SA07358719Naïve NLRP6KO Small Intestine lumen
SA0735887Naïve WT Large Intestine lumen
SA0735896Naïve WT Large Intestine lumen
SA0735905Naïve WT Large Intestine lumen
SA0735914Naïve WT Large Intestine lumen
SA0735928Naïve WT Large Intestine lumen
SA07359323Naïve WT Small Intestine lumen
SA07359421Naïve WT Small Intestine lumen
SA07359520Naïve WT Small Intestine lumen
SA07359622Naïve WT Small Intestine lumen
SA07359724Naïve WT Small Intestine lumen
Showing results 1 to 32 of 32

Collection:

Collection ID:CO001127
Collection Summary:Stool lumen contents
Sample Type:Intestinal lumen contents

Treatment:

Treatment ID:TR001147
Treatment Summary:BMT from naive [B6Ly5.2→B6] and allogenic e allogeneic [B6Ly5.2→Nlrp6-/-] animals

Sample Preparation:

Sampleprep ID:SP001140
Sampleprep Summary:To determine targeted taurine quantitation, samples (int estinal fecal content) from mice 21d post-transplant were harvested, homogenized, and snap-frozen in liquid N2. Fecal content was we ighed at necropsy. Samples were extracted with acetonitrile spiked with stable isotope-labeled C13 taurine standards. The supernatan t was analyzed by Agilent 6490 mass spectrometer in a positive electrospray ionization mode after liquid chromatography using a HILI C mode and isocratic gradient. Quantitation was performed by calibration to internal standards and expressed in mM after normalizati on for weights.

Chromatography:

Chromatography ID:CH001254
Instrument Name:Agilent 1290 Infinity
Column Name:Phenomenex Kinetex HILIC 100A (50 x 2.1 mm,2.6um)
Chromatography Type:HILIC

Analysis:

Analysis ID:AN001774
Analysis Type:MS
Chromatography ID:CH001254
Num Factors:8
Num Metabolites:1
Rt Units:Minutes
Units:M/100mg stool
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