# Metabolic perturbations in conventional dendritic cells modulate Tfh13 induction in asthmatic sensitization

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $594,338

## Abstract

Abstract
Allergic asthma is among the most common chronic lung diseases worldwide, and despite advances in
treatment asthma prevalence continues to rise globally. Allergic asthma is largely driven by IgE
antibodies that target environmental allergens. The production of allergen-specific IgE requires T
follicular helper 13 cells (Tfh13) which must first be polarized by dendritic cells (DCs). However, a
critical knowledge gap remains: how do DCs gain the ability to induce Tfh13s? By studying DC
responses to allergic stimuli, we have determined that allergens induce a unique metabolic program in
DCs, characterized by increased glutamine metabolism. We identified that allergen stimulated DCs
exhibit aberrant TCA cycle metabolism, which leads to accumulation of α-ketoglutarate and succinate
and reduced levels of fumarate and malate. We hypothesize that DC glutamine metabolism after
allergen exposure is critical for polarization of Tfh13s. The goals of this proposal are (1) to
ascertain effector mechanisms downstream of glutamine metabolism that induce Tfh13 polarization, (2)
to elucidate key mechanistic changes in DCs induced by aberrant TCA cycle metabolites, and (3) to
determine the translatability of this pathway into human DCs. This work promises an exciting new
avenue for development of novel therapeutic targets and preventive strategies for the management of
allergic asthma.

## Key facts

- **NIH application ID:** 10757625
- **Project number:** 5R01HL162991-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Rebecca Kelley Martin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $594,338
- **Award type:** 5
- **Project period:** 2022-12-25 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10757625

## Citation

> US National Institutes of Health, RePORTER application 10757625, Metabolic perturbations in conventional dendritic cells modulate Tfh13 induction in asthmatic sensitization (5R01HL162991-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10757625. Licensed CC0.

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