Prophylactic Peanut Allergen Ara h 6 Sublingual Immunotherapy Drives Expansion of FoxP3+Helios Regulatory T Cells in the Absence of Allergen-Specific IgA

Jeppe Madura Larsen*, Emma Alberte Lundsgaard, Niels Banhos Danneskiold-Samsøe, Si Brask Sonne, Neil Marcus Rigby, Alan Robert Mackie, Karsten Kristiansen, Katrine Lindholm Bøgh

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Insights into the underlying immunological mechanisms of prophylactic sublingual immunotherapy (SLIT) may support the development of new strategies for improved prevention and treatment of food allergy. Here, we investigated the humoral, regulatory and sublingual tissue immune response to prophylactic SLIT administration of a single purified peanut allergen in Brown Norway (BN) rats. BN rats received daily sublingual administration of peanut allergen Ara h 6 for three weeks. Suppression of sensitisation was evaluated by subsequent intraperitoneal administration of Ara h 6. Ara h 6-specific IgE, IgA, IgG1 and IgG2a-c levels were measured in serum. The frequency of regulatory T (Treg) cells was analysed using flow cytometry. The sublingual tissue response to Ara h 6 was analysed by transcriptional profiling using mRNA-sequencing. Ara h 6 SLIT protected rats from subsequent sensitisation without inducing a detectable humoral immune response (Ara h 6-specific IgE, IgA, IgG1 and IgG2a-c) in serum. SLIT furthermore promoted the relative expansion of induced Helios Treg cells within the conventional CD4+CD25+FoxP3+ Treg population in sublingual draining lymph nodes and blood. In conclusion, prophylactic Ara h 6 SLIT drives the relative expansion of induced Helios Treg cells in the absence of Ara h 6-specific IgA highlighting a potential novel IgA-independent Treg-related immune response at the sublingual mucosal site.

Original languageEnglish
JournalImmunology
Volume174
Issue number3
Pages (from-to)340-348
Number of pages9
ISSN0019-2805
DOIs
Publication statusPublished - 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Immunology published by John Wiley & Sons Ltd.

Keywords

  • immune response
  • peanut allergy
  • prophylaxis
  • sublingual immunotherapy
  • tissue response

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