Subcutaneous immunotherapy-induced IgG1 suppresses allergic airway inflammation through FcγRIIb-mediated inhibition of group 2 innate lymphoid cell proliferation.

Background: Subcutaneous immunotherapy (SCIT), a form of allergy immunotherapy, can alter the natural course of allergic diseases and induce tolerance to causative allergens by modulating type 2 immune responses. While the regulatory effects of SCIT on Th2 cells have been extensively studied, its effects on group 2 innate lymphoid cells (ILC2s) remain poorly understood. In a murine model of asthma, we demonstrated that SCIT increased the production of allergen-specific IgG1, which is analogous to human IgG4. To clarify the role of IgG1 in the mechanisms underlying SCIT, we evaluated its effects on the development of allergic asthma and the proliferation of ILC2s. Methods: BALB/c mice were sensitized with ovalbumin (OVA) and Al(OH) Results: (1) IgG1 Conclusions: SCIT-IgG1 attenuates airway remodeling and limits ILC2 expansion in allergic airway inflammation. Mechanistically, SCIT-IgG1 restrains ILC2 proliferation via FcγRIIb engagement, revealing an antibody-ILC2 inhibitory axis that likely contributes to the efficacy of allergy immunotherapy and suggests therapeutic strategies that enhance inhibitory FcγR signaling to control type 2 inflammation.