Notch2-expressing regulatory T cells attenuate allergic rhinitis by downregulating MHC class II expression on...

To investigate the role of Notch2-expressing regulatory T cells (Notch2⁺ Tregs) in modulating the function of dendritic cells (DCs) and their impact on the development of allergic rhinitis (AR).

Peripheral blood mononuclear cells (PBMC) from patients with allergic rhinitis (AR) and Control groups were analyzed by flow cytometry to quantify Notch2⁺ Tregs. Murine T cells were isolated and transduced with a lentiviral vector overexpressing Notch2 to assess changes in the immunosuppressive function of Tregs. Scanning electron microscopy (SEM) was performed to visualize the morphological interactions between Tregs and Bone marrow-derived dendritic cells (BMDCs). BMDCs were cocultured with Notch2-overexpressing or control Tregs in direct-contact and Transwell coculture systems to evaluate changes in surface MHC class II (MHC II) expression. In vivo, Notch2-overexpressing Tregs were adoptively transferred into a conventional AR mouse model, after which the Treg and DC frequencies, surface MHC II expression, and allergic inflammatory responses were assessed.

Patients with AR had a significantly lower frequency of peripheral Notch2⁺ Tregs than controls (P < 0.01), and Notch2⁺ Treg frequency was negatively correlated with allergen-specific IgE levels and TNSS (P < 0.01). In vitro, Notch2 enhanced the immunosuppressive function of Tregs, increased MHC II expression on Tregs, and decreased MHC II expression on DCs. In vivo, adoptive transfer of Notch2-overexpressing Tregs significantly alleviated allergic inflammation in AR mice by reducing MHC II expression on DCs (P < 0.05).

Notch2 attenuates allergic inflammation in AR by enhancing Treg immunosuppressive function and downregulating MHC II expression on DCs. Notch2 in Tregs may represent a novel therapeutic target for allergic airway diseases.