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In Vivo Augmentation of Gut-Homing Regulatory T Cell Induction
Published on: January 22, 2020
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Microbiota-induced regulatory T cells associate with FUT2-dependent susceptibility to rotavirus gastroenteritis
Emmanuelle Godefroy1, Laure Barbé1, Béatrice Le Moullac-Vaidye1
1Inserm, CNRS, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1303/EMR6001, Nantes Université, Nantes, France.
Frontiers in Microbiology
|March 16, 2023
Summary
The FUT2 gene influences rotavirus gastroenteritis risk and gut microbiota composition. The wild-type FUT2 allele links to rotavirus antibodies and regulatory T cells, potentially protecting against inflammatory diseases.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- The FUT2 enzyme synthesizes fucosylated glycans, crucial for pathogen attachment like noroviruses and rotaviruses (RVAs), causing childhood gastroenteritis.
- FUT2 genetic variations impact RVA susceptibility and resistance, with the wild-type allele linked to susceptibility but paradoxically associated with protection against inflammatory diseases.
- FUT2's role in microbiota composition is known, but its specific link to immune responses and inflammatory conditions remains unclear.
Purpose of the Study:
- To investigate the association between the wild-type FUT2 allele, rotavirus gastroenteritis risk, gut microbiota, and regulatory T cell induction in healthy adults.
- To explore the connection between FUT2 genotype, anti-RVA antibody presence, and the frequency of gut microbiota-induced DP8α regulatory T cells (Tregs).
- To determine if Faecalibacterium prausnitzii abundance correlates with the FUT2 wild-type allele and DP8α Treg induction.
Main Methods:
- Studied a cohort of young healthy adults.
- Assessed the association between FUT2 genotype and the presence of anti-RVA antibodies (neutralizing and IgA).
- Quantified the frequency of gut microbiota-induced DP8α Tregs and fecal F. prausnitzii proportion.
Main Results:
- The wild-type FUT2 allele was associated with the presence of anti-RVA antibodies, confirming its link to RVA gastroenteritis risk.
- Wild-type FUT2 allele correlated with DP8α Treg frequency, specifically in individuals with anti-RVA antibodies.
- Fecal abundance of F. prausnitzii was also associated with the wild-type FUT2 allele.
Conclusions:
- The FUT2 genotype links RVA gastroenteritis risk, gut microbiota composition, and DP8α Treg induction.
- The anti-RVA immune response may involve DP8α Tregs, potentially induced by F. prausnitzii.
- This mechanism suggests a pathway where FUT2 influences immune balance, conferring protection against inflammatory diseases.
Keywords:
FUT2Faecalibacterium prausnitziiantibodiesfucosylationhisto-blood group antigensinflammatory diseasesregulatory T cellsrotavirusMore Related Videos
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