Mechanisms of TFR cell-mediated regulation of microbiota-reactive IgA responses

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B108
Abstract ID: 5510

Presenting Author:
Abdullahi M Abdi , Ph.D. Candidate at Indiana Univ. Sch. of Med.

Abstract:

The rising prevalence of food allergies impacting over 10% of the U.S. population requires innovative diagnostic approaches and therapeutic interventions. Gut microbiota alterations play a crucial role in food allergy development, with immunoglobulin IgA (IgA) actively regulating gut microbiome composition. While T follicular helper (TFH) cells aid in high-affinity antigen-specific IgA production, T follicular regulatory (TFR) cells' role in generating microbiota-specific IgA remains unclear. Using a unique TFR cell-deficient mouse model (Bcl6FC) and flow cytometry staining, we found increased fecal IgA-coated bacteria over time in Bcl6FC compared to WT mice after sensitization. IgA-seq revealed differential baseline microbiota IgA-coating in naïve Bcl6FC, displaying increased alpha diversity and more taxa with higher relative abundance than WT mice. Calculating the IgA-index demonstrated elevated IgA binding in Bcl6FC mice to specific taxa, primarily Firmicute members, indicating TFR cells' suppression of taxon-specific IgA in the peanut allergy model. Ongoing experiments, including the adoptive transfer of WT TFR cells into Bcl6FC mice and the assessment of IgA-coated biome function via Fecal Microbiota Transplantation (FMT) into germ-free mice in a peanut allergy model, aim to validate TFR cells' role in generating microbiota-specific IgA responses. This contributes essential insights for potential therapeutic antibodies targeting specific commensals.