Altered microbial bile acid metabolism exacerbates T cell-driven inflammation during GVHD

About this publication:

Sarah Lindner, PhD, and colleagues investigate the relationship between microbial transformation of bile acids, intestinal immune homeostasis, and inflammatory pathologies. By using a model of graft-versus-host disease (GVHD), the authors were able to determine that T cell-driven inflammation decreased the abundance of microbe-derived metabolites, which are important in reducing T cell-mediated disease.

Publication Summary

Authors Lindner et al. investigate how changes in bile acid metabolism by gut microbiota can worsen inflammation caused by T cell responses during graft-versus-host disease (GVHD), and how alterations of T cell-mediated responses can result in inflammatory pathologies.  One approach used in this model was to assess ligand-dependent signaling and associated activation and  proliferation of T cells through single-cell sequencing. The researchers demonstrate how alterations in bile acid composition impacts immune responses and disease severity in GVHD mouse models. By elucidating the interplay between microbiota, bile acids, and T cell-mediated inflammation, this study sheds light on potential therapeutic targets for managing GVHD.

Levitation Technology Enriches for Viable T-Cells

 In order to get the best possible results, the removal of dead/dying cells  and debris is critical, as these contaminants can hinder accurate cell counts, impact experimental design, increase expenditure of resources, and complicate data analysis and interpretation. To address this, the authors utilized Levitation Technology(™) as a means to gently enrich viable T cells and remove contaminants, without the need for antibodies or dyes. By achieving >80% viability for their samples, they were able to generate high-quality data and run single-cell RNA seq expression analysis  with confidence. Based on their findings, the authors were able to identify a potential role for FXR targeting as a means to modulate T cell driven pathologies.