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Updated: Jul 7, 2026
09:51
Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Dendritic Cell α-Ketoglutarate Regulates Tfh Polarization in Allergy
Anuj Tharakan1, Xufeng Qu2, Carmen Camarena3
1Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, Virginia, USA.
Allergy
|July 6, 2026
Summary
Allergen exposure activates specific Tfh13 cells via cDC2 metabolic changes, increasing alpha-ketoglutarate. Inhibiting this pathway suppresses allergic responses and IgE production, offering a new therapeutic target for allergies.
Area of Science:
- Immunology
- Metabolic pathways
- Allergic disease mechanisms
Background:
- Allergic responses are initiated by T follicular helper (Tfh) cells, specifically Tfh13 cells.
- Naïve CD4+ T cell differentiation into Tfh13 cells is induced by antigen-presenting cells like type 2 conventional dendritic cells (cDC2s) after allergen exposure.
Purpose of the Study:
- To investigate the metabolic reprogramming of cDC2s during allergic sensitization.
- To elucidate the role of glutamine metabolism and alpha-ketoglutarate in Tfh13 cell differentiation and allergic responses.
Main Methods:
- Analysis of cDC2 metabolic programs following allergen stimulation.
- Inhibition of glutaminolysis and assessment of Tfh13 and T follicular regulatory (Tfr) cell populations in vivo.
- Investigation of alpha-ketoglutarate's role in modulating JmjD3 and HIF-1α activity.
- Pharmacological inhibition of glutaminase or HIF-PH in allergen-sensitized mouse models.
Main Results:
- Allergen stimulation increases glutaminolysis and alpha-ketoglutarate accumulation in cDC2s.
- Glutaminolysis inhibition suppressed Tfh13 differentiation and promoted Tfr cell activation.
- Alpha-ketoglutarate regulates Tfh13 polarization via JmjD3 and HIF-1α.
- Inhibitor treatment in mice induced allergen tolerance, reducing asthma symptoms and IgE production.
Conclusions:
- Alpha-ketoglutarate production by cDC2s is critical for allergic sensitization by driving Tfh13 cell differentiation and IgE production.
- The glutaminase 1-JmjD3/HIF-PH axis is a key regulator of allergic responses.
- Targeting this axis offers a potential therapeutic strategy for IgE-mediated allergic diseases.
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