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In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction
Published on: January 22, 2020
Triggering the succinate receptor GPR91 on dendritic cells enhances immunity
Tina Rubic1, Günther Lametschwandtner, Sandra Jost
1Novartis Institutes for Biomedical Research, Vienna A-1235, Austria.
Nature Immunology
|September 30, 2008
Summary
Succinate, a cellular respiration metabolite, signals through GPR91. This receptor on dendritic cells links metabolism to immunity, impacting T cell responses and transplant rejection.
Area of Science:
- Immunology
- Metabolism
- Cellular Signaling
Background:
- Succinate functions as an extracellular signaling molecule via the G protein-coupled receptor GPR91.
- Dendritic cells exhibit high expression levels of GPR91.
Purpose of the Study:
- To investigate the role of succinate and its receptor GPR91 in immune responses.
- To explore the link between cellular metabolism and immune cell activation.
Main Methods:
- Assessed GPR91 expression in dendritic cells.
- Stimulated cells with succinate and measured calcium mobilization, migration, and cytokine production.
- Evaluated T cell activation and immune responses in GPR91-deficient mice.
- Analyzed transplant rejection in GPR91-deficient allografts.
Main Results:
- Succinate triggered calcium mobilization and migration in dendritic cells expressing GPR91.
- Succinate synergized with Toll-like receptor ligands to promote pro-inflammatory cytokine production.
- Succinate enhanced antigen-specific helper T cell activation.
- GPR91 deficiency led to reduced Langerhans cell migration and impaired T cell recall responses.
- GPR91-deficient allografts showed reduced transplant rejection.
Conclusions:
- The succinate receptor GPR91 is crucial for sensing immunological danger.
- GPR91 establishes a critical link between cellular respiration metabolites and immune system function.
- Targeting the succinate-GPR91 axis may offer therapeutic strategies for immune modulation.
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