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

Introduction: 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. Methods: 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. Results: 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-g 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. Discussion: 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.