Immunosuppressive Regulation of Dendritic Cells and T Cells in Allergic Rhinitis by Semaphorin 3A

Abstract

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.

Update on pathomechanisms and treatments in allergic rhinitis

“…DCs are divided into different subsets including CD11c + mDC and CD123 + plasmacytoid DC (pDC), which are present in the human airway circulation during the disease 53 . Increasing evidence suggests that the enhanced antigen‐presenting function of mDC in the OVA‐sensitized AR mouse model or AR patients was associated with enhanced autophagy 54 and high expression levels of the maturation markers CD40 and CD83 in DCs 55 . Additionally, HDM challenge has been shown to promote IL‐33 release from mDCs to aggregate local inflammation in HDM‐sensitized AR patients 5,56 .…”

To Think Outside the Box Requires Stepping Outside of Your Comfort Zone

“…Our basic understanding of the immunologic changes and their impact on the pathophysiology of sinus disease continues to evolve as evidenced by numerous works presented. [1][2][3][4] Environmental exposures and changing climate may be playing a role. Airborne pollutant material has been associated with pulmonary and cardiovascular problems.…”