Low-dose allergen targeting to cDC2 induces long-term protection associated with induction of regulatory-like IL-10+ Foxp3- CD8+ T cells in mice

Aintablian A, Cyran L, Helal M, Lehmann C, Imdahl F, Gräfenhan T, Riedel A, Dudziak D, Kerstan A, Lutz MB (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 17

Pages Range: 1846923-

DOI: 10.3389/fimmu.2026.1846923

Abstract

The prevalence of allergic diseases is rising worldwide. Desensitizing immunotherapy is currently the only available treatment, but it is often ineffective for certain allergies, underscoring the need for new treatments. This study tested in an Ovalbumin (OVA)-mediated allergy mouse model whether direct allergen targeting to DC subsets can induce desensitization. A Standard desensitization protocol was compared with an antibody-OVA fusion protein targeting the conventional cDC1 or cDC2 subsets via their respective receptors CD205 (CD205-Fp) or DCIR2 (DCIR2-Fp). Allergen targeting to cDC2 provided long-lasting protection for up to 56 days after desensitization with only nanogram doses of allergen, whereas the Standard therapy protected for only 20 days, requiring microgram doses and repeated injections with Alum adjuvant. CD205-Fp showed no protective effect. Blocking IL-10 either before administering DCIR2-Fp or before allergen challenge completely abolished protection. Standard therapy had moderate effects on CD4+ T cells, with early expansion of IL-10+ Foxp3- T regulatory type-1 cells (Tr1), followed by an increase in both IL-10+ and IL-10- Foxp3+ regulatory T cells (Foxp3+ Treg). DCIR2-Fp therapy initially expanded IL-10+ and IL-10- Foxp3+ Treg, but these levels returned to baseline. On day 80, we identified Foxp3- CD44high Treg-like CD8+ as the primary source of IL-10. Overall, our data suggest that cDC2 allergen targeting in allergic mice offers a potent, long-lasting IL-10-dependent desensitizing effect.

Authors with CRIS profile

Christian Lehmann Department of Dermatology Diana Dudziak Professur für die Biologie Dendritischer Zellen

Involved external institutions

Julius-Maximilians-Universität Würzburg DE Germany (DE) Universitätsklinikum Würzburg DE Germany (DE) Helmholtz-Institut für RNA-basierte Infektionsforschung (HIRI) DE Germany (DE)

How to cite

APA:

Aintablian, A., Cyran, L., Helal, M., Lehmann, C., Imdahl, F., Gräfenhan, T.,... Lutz, M.B. (2026). Low-dose allergen targeting to cDC2 induces long-term protection associated with induction of regulatory-like IL-10+ Foxp3- CD8+ T cells in mice. Frontiers in Immunology, 17, 1846923-. https://doi.org/10.3389/fimmu.2026.1846923

MLA:

Aintablian, Arpa, et al. "Low-dose allergen targeting to cDC2 induces long-term protection associated with induction of regulatory-like IL-10+ Foxp3- CD8+ T cells in mice." Frontiers in Immunology 17 (2026): 1846923-.

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