100063 - Nasal ST2⁺ regulatory T cells restrain Tc1-Neutrophil axis in 1 chronic rhinosinusitis

Regulatory T cells (Tregs) maintain mucosal homeostasis, yet their roles in the nasal mucosa and chronic rhinosinusitis (CRS) are incompletely defined. We identify tissue-resident ST2⁺ nasal Tregs as pivotal regulators of local immunity.

An aspergillus protease and ovalbumin-induced chronic inflammation model to investigate the impact of Treg cells on CRS. Korean adult patients with CRSwNPs and healthy controls were enrolled from the Department of Otorhinolaryngology - Head and Neck Surgery, Asan Medical Center (AMC) between September 2022 and May 2025. 

Single-cell and spatial profiling showed that Tregs suppress Tc1-driven IFN-γ production and neutrophil recruitment, limiting tissue injury. Genetic ablation of ST2 in Tregs exacerbated sinonasal inflammation, unleashing pathogenic CD8⁺ T cells and neutrophils. Conversely, intranasal adeno-associated viral delivery of an IL-2 mutein selectively expanded nasal Tregs and ameliorated neutrophil dominant disease without systemic activation. In CRS patients, biologic therapy increased

activated ST2⁺ and CD39⁺ Tregs, correlating with symptom improvement and reduced effector CD8⁺ subsets. 

These findings establish nasal ST2⁺ Tregs as a tissue-resident checkpoint for upper airway immunity that restrains Tc1-neutrophil inflammation and highlight their targeted expansion as a promising therapeutic strategy for refractory airway disease.