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Suppression of NF-κB and downstream XBP1 by DcR3 contributes to a decrease in antibody secretion
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DOI：10.1093/jimmun/vkae005.png)
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Abstract
En 中文
Decoy receptor 3 (DcR3), a soluble receptor in the tumor necrosis factor receptor superfamily, regulates the functions of monocytes, macrophages, dendritic cells, and T cells. Previous studies have demonstrated that DcR3 suppresses B cell proliferation in vitro and ameliorates autoimmune diseases in animal models; however, whether and how DcR3 regulates antibody production is unclear. Using a DcR3 transgenic mouse model, we found that DcR3 impaired the T cell-dependent antigen-stimulated antibody response. The number of Ag-specific antibody-secreting cells was transiently reduced, but the concentration of specific antibodies continued to decrease in the DcR3 transgenic mice, implying a direct suppression of antibody production by DcR3. In vitro assays showed that the DcR3-Fc fusion protein attenuated T cell-dependent induced antibody production and reduced the expression of secretory Igh and Xbp1. We found that nuclear factor kappa B (NF-kappa B) activity was essential for the expression of Xbp1 in activated B cells. DcR3-Fc attenuated anti-CD40-induced NF-kappa B activity and Xbp1 promoter activity. Furthermore, DcR3-Fc decreased the expression of Xbp1 in Blimp1+ antibody-secreting cells. Restoration of spliced XBP1 (X-box binding protein 1) in DcR3-treated B cells increased the secretory Ighg1 transcript levels, suggesting that reducing XBP1 is one of the mechanisms by which DcR3 regulates antibody production both in vitro and in vivo. Collectively, these results indicate that in addition to blocking proliferation, DcR3 impairs NF-kappa B activation, subsequently decreasing the expression of Xbp1, eventually leading to a reduction in antibody secretion.
Keywords:
antibody secretion
decoy receptor 3
humoral response
NF-kappa B
X-box binding protein 1
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3.4
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