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Background Parasympathetic nerve hypersensitivity contributes to the severity of allergic rhinitis (AR), but the precise mechanism underlying neuroimmune regulation in patients with AR remains unclear. This study investigated the effect of cholinergic nerve inhibition on AR CD4+ T‐helper (Th)2‐cell polarization and the underlying regulatory mechanism in vitro. Methods An in‐vitro neuroimmune coculture model of D‐U87 cells and CD4+ T cells was established. D‐U87 cells with cholinergic neuron characteristics were used as cholinergic neuron models. CD4+ T cells were derived from peripheral blood monocytes from AR patients (n = 60) and control subjects (n = 40). Th1‐ and Th2‐cell percentages were measured by flow cytometry. Proteins involved in related signaling pathways were analyzed by protein chip assay and Western blotting. Results The Th2‐cell percentage among CD4+ T cells from AR patients was significantly increased after coculture with D‐U87 cells and was decreased by ipratropium bromide (IB) treatment. In contrast, the Th1‐cell percentage among control CD4+ T cells was significantly increased after coculture with D‐U87 cells, but was unaltered by IB treatment. Furthermore, phosphorylated Akt (p‐Akt) protein levels increased in CD4+ T cells from both controls and AR patients after coculture with D‐U87 cells and decreased after IB treatment. However, higher p‐Akt levels were observed in cells from AR patients than in cells from control subjects. Moreover, Akt inhibition decreased Th2‐cell percentage in AR patients. Conclusion In‐vitro cholinergic nerve inhibition with IB decreased AR CD4+ T‐cell polarization into Th2 cells partially through an Akt‐dependent mechanism.

Background Semaphrin3A (Sema3A) was found to play a major role in immune regulation in autoimmune diseases and to be of importance in allergic disease. However, the effect of Sema3A on allergic rhinitis (AR) is not fully clear. Objective We sought to elucidate the effects of Sema3A on the regulation of dendritic cells (DCs) and naive CD4+ T cells in AR. Methods The expression of Sema3A in nasal mucosa was measured by immunohistochemical staining and western blotting. Human peripheral blood mononuclear cells were separated by the Ficoll-Hypaque method. DCs and naive CD4+ T cells were purified by magnetic selection. A human Sema3A Fc chimera was added to DCs and naive CD4+ T cells in vitro to evaluate the effect of Sema3A on the function of DCs and T cells. Labeling T cells with CFSE was used to determine cell proliferation. Flow cytometry was used to detect the DC maturation markers (CD40 and CD83) and T helper 17 (Th17) and regulatory T cell (Treg) percentages. ELISA was used to detect the IL10, IL17, IL4, and IFNγ cytokine levels. Results The expression of Sema3A in AR inferior turbinate tissue was lower than that in healthy control tissue. Compared with healthy control DCs, AR DCs showed decreased levels of the DC maturation markers CD40 and CD83 after Sema3A treatment. Furthermore, Sema3A decreased naive CD4+ T cell proliferation in AR. In addition, Sema3A increased the percentage of Tregs but had no obvious effect on Th17 cells. Moreover, Sema3A significantly increased levels of IL10 and IFNγ, and decreased level of IL4, but had no obvious effect on level of IL17. Conclusion AR presented with low expression of Sema3A in nasal mucosa, and Sema3A could decrease DC maturation, T cell proliferation, and Treg polarization.