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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST001089 |
| Study Title | Host NLRP6 exacerbates graft-versus-host disease independent of microbial diversity |
| Study 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 |
| amat@umich.edu | |
| Phone | 7342328228 |
| Submit Date | 2018-11-05 |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2019-10-11 |
| Release Version | 1 |
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Subject:
| Subject ID: | SU001133 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Genotype Strain: | B6Ly5.2 |
