Microbial metabolite sensor GPR43 controls severity of experimental GVHD Journal Article

Authors: Fujiwara, H.; Docampo, M. D.; Riwes, M.; Peltier, D.; Toubai, T.; Henig, I.; Wu, S. J.; Kim, S.; Taylor, A.; Brabbs, S.; Liu, C.; Zajac, C.; Oravecz-Wilson, K.; Sun, Y.; Núñez, G.; Levine, J. E.; van den Brink, M. R. M.; Ferrara, J. L. M.; Reddy, P.
Article Title: Microbial metabolite sensor GPR43 controls severity of experimental GVHD
Abstract: Microbiome-derived metabolites influence intestinal homeostasis and regulate graft-versus-host disease (GVHD), but the molecular mechanisms remain unknown. Here we show the metabolite sensor G-protein-coupled receptor 43 (GPR43) is important for attenuation of gastrointestinal GVHD in multiple clinically relevant murine models. GPR43 is critical for the protective effects of short-chain fatty acids (SCFAs), butyrate and propionate. Increased severity of GVHD in the absence of GPR43 is not due to baseline differences in the endogenous microbiota of the hosts. We confirm the ability of microbiome-derived metabolites to reduce GVHD by several methods, including co-housing, antibiotic treatment, and administration of exogenous SCFAs. The GVHD protective effect of SCFAs requires GPR43-mediated ERK phosphorylation and activation of the NLRP3 inflammasome in non-hematopoietic target tissues of the host. These data provide insight into mechanisms of microbial metabolite-mediated protection of target tissues from the damage caused allogeneic T cells. © 2018, The Author(s).
Keywords: murinae
Journal Title: Nature Communications
Volume: 9
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2018-09-10
Start Page: 3674
Language: English
DOI: 10.1038/s41467-018-06048-w
PROVIDER: scopus
PMCID: PMC6131147
PUBMED: 30201970
Notes: Article -- Export Date: 1 October 2018 -- Source: Scopus
Citation Impact
MSK Authors
  1. Melissa   Docampo
    17 Docampo