Abstract
Restoration of the antigen (Ag)-specific immune tolerance in an allergic environment is refractory. B cells are involved in immune regulation. Whether B cells facilitate the generation of Ag-specific immune tolerance in an allergic environment requires further investigation. This paper aims to elucidate the mechanism by which B cells restore the Ag-specific immune tolerance in an allergic environment. In this study, a B cell-deficient mouse model was created by injecting an anti-CD20 antibody. The frequency of tolerogenic dendritic cell (TolDC) was assessed by flow cytometry. The levels of cytokines were determined by enzyme-linked immunosorbent assay. The expression of thrombospondin-1 (TSP1) was assessed by quantitative real-time RT-PCR, Western blotting, and methylation-specific PCR. The results showed that B cells were required in the generation of the TGF-β-producing TolDCs in mice. B cell-derived TSP1 converted the latent TGF-β to the active TGF-β in DCs, which generated TGF-β-producing TolDCs. Exposure to IL-13 inhibited the expression of TSP1 in B cells by enhancing the TSP1 gene DNA methylation. Treating food allergy mice with Ag-specific immunotherapy and IL-13 antagonists restored the generation of TolDCs and enhanced the effect of specific immunotherapy. In conclusion, B cells play a critical role in the restoration of specific immune tolerance in an allergic environment. Blocking IL-13 in an allergic environment facilitated the generation of TolDCs and enhanced the therapeutic effect of immunotherapy.
Highlights
The generation of tolerogenic dendritic cells (TolDCs) in an allergic environment is refractory
The mice were treated with Modified Ag-specific Immunotherapy (MSIT) for 6 days; the results showed that the frequency of TolDCs was markedly increased (p Ͻ 0.01) in the intestine as compared with those sensitized mice treated with saline (Fig. 6, D, E, and J)
The present data show that the B cell-derived TSP1 is required in the generation of transforming growth factor (TGF)-ϩ TolDCs in an allergic environment
Summary
The generation of tolerogenic dendritic cells (TolDCs) in an allergic environment is refractory. Conclusion: Blocking IL-13 in an allergic environment facilitates the generation of TolDCs. Significance: Using IL-13 antagonists has the potential to enhance the therapeutic effect of the allergic diseases. Restoration of the antigen (Ag)-specific immune tolerance in an allergic environment is refractory. Whether B cells facilitate the generation of Ag-specific immune tolerance in an allergic environment requires further investigation. This paper aims to elucidate the mechanism by which B cells restore the Ag-specific immune tolerance in an allergic environment. Treating food allergy mice with Ag-specific immunotherapy and IL-13 antagonists restored the generation of TolDCs and enhanced the effect of specific immunotherapy. B cells play a critical role in the restoration of specific immune tolerance in an allergic environment. Blocking IL-13 in an allergic environment facilitated the generation of TolDCs and enhanced the therapeutic effect of immunotherapy
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