# Modulation of type 2 inflammation during grass pollen-specific sublingual immunotherapy

**Authors:** Lorenzo Salvati, Manuela Capone, Alessio Mazzoni, Anna Vanni, Giulia Lamacchia, Cristina Scaletti, Paola Parronchi, Francesco Liotta, Francesco Annunziato, Lorenzo Cosmi, Laura Maggi

PMC · DOI: 10.3389/fimmu.2026.1784244 · Frontiers in Immunology · 2026-03-09

## TL;DR

This study shows that grass pollen-specific sublingual immunotherapy reduces type 2 immune responses in allergic rhinitis patients, leading to long-term clinical improvement.

## Contribution

The study provides new insights into the immunological mechanisms of sublingual immunotherapy in modulating type 2 inflammation.

## Key findings

- Frequencies of IL-4 and IL-13 producing CD4+ T cells decreased after one year of treatment.
- Clinical improvement was sustained over three years despite stable grass-specific IgE levels.
- IFN-γ producing CD4+ T cells remained stable during the treatment period.

## Abstract

Both ILC2 and Th2 cell subsets play a critical role as functional effector cells in the pathogenesis of allergic diseases. Although allergen-specific immunotherapy is currently the only disease-modifying therapy available for allergic disorders, the immunological mechanisms interfering with type 2 immune response are not yet fully explored.

This study focuses on describing the immunological changes caused by standardized grass pollen-specific sublingual immunotherapy (SLIT) in a cohort of patients with seasonal allergic rhinitis. Patients diagnosed with moderate to severe seasonal allergic rhinitis were enrolled and treated with grass pollen-specific SLIT for a duration of three years. We investigated circulating CD4+ T cells and ILC2 via flow-cytometry, assessing their cytokine expression. Grass-specific IgE levels were assessed.

We observed a decrease of frequencies of IL-4 and IL-13 producing, and CD154-expressing, CD4+ T cells after one year of treatment, while frequencies of IFN-γ producing CD4+ T remained stable. We also observed significant and long-term clinical improvement induced by SLIT, although grass-specific IgE levels remained relatively stable over time.

These exploratory findings collectively suggest early modulation of the type 2 immune response with sustained clinical response regardless of persistent allergic sensitization in patients undergoing grass pollen-specific SLIT for allergic rhinitis.

## Linked entities

- **Proteins:** IL4 (interleukin 4), IL13 (interleukin 13), CD40LG (CD40 ligand), IFNG (interferon gamma), IGHE (immunoglobulin heavy constant epsilon)
- **Diseases:** allergic rhinitis (MONDO:0011786)

## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, IGHE (immunoglobulin heavy constant epsilon) [NCBI Gene 3497] {aka IgE}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, CD40LG (CD40 ligand) [NCBI Gene 959] {aka CD154, CD40L, HIGM1, IGM, IMD3, T-BAM}
- **Diseases:** seasonal allergic rhinitis (MESH:D006255), allergic rhinitis (MESH:D065631), type 2 inflammation (MESH:D007249), allergic diseases (MESH:D004342)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13006293/full.md

## References

35 references — full list in the complete paper: https://tomesphere.com/paper/PMC13006293/full.md

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Source: https://tomesphere.com/paper/PMC13006293