Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities.Here we revealed the immunosuppressive effect of folic a...Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities.Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B(MZB)cells.Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M(IgM),targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor(BCR)complex and block immune responses.The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens.Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies,which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions.Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies,and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.展开更多
The biological activity of the multifunctional cytokine interleukin-1 （IL-1） is mediated by its receptors. The aim of this study was to determine if an association exists between single nucleotide polymorphisms （S...The biological activity of the multifunctional cytokine interleukin-1 （IL-1） is mediated by its receptors. The aim of this study was to determine if an association exists between single nucleotide polymorphisms （SNPs） in the IL-1 type I and 2 receptor genes （ILIR1 and ILIR2） and the expression level of membrane-bound ILIRs on subpopulations of mononuclear cells or serum levels of soluble IL-1 receptors. It was observed that healthy individuals with the genotype TT in SNP rs2234650.C〉T had a lower percentage of intact CD14＋ monocytes expressing ILIR1 on their surface. The SNP rs4141134-T〉C in ILIR2 has also been associated with the percentage of intact CD3＋ T cells expressing ILIR2. Furthermore, individuals carrying the CC allele of SNP rs4141134.T〉C and the TT allele of SNP rs2071008-T〉G in ILIR2 had a lower density of ILIR2s on the surface of CD14＋ monocytes in lipopolysaccharide （LPS）-stimulated PBMC cultures. In summary, this study demonstrated that IL-1 receptor gene polymorphisms could be one of the factors influencing the expression of membrane-bound IL-1 receptors （ILIR） on immunocompetent cells.展开更多
基金supported by the National Natural Science Foundation of China(82125035,81973245 and 82373817,China)Shanghai Education Commission Major Project(2021-01-07-00-07-E00081,China)。
文摘Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities.Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B(MZB)cells.Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M(IgM),targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor(BCR)complex and block immune responses.The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens.Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies,which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions.Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies,and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.
文摘The biological activity of the multifunctional cytokine interleukin-1 （IL-1） is mediated by its receptors. The aim of this study was to determine if an association exists between single nucleotide polymorphisms （SNPs） in the IL-1 type I and 2 receptor genes （ILIR1 and ILIR2） and the expression level of membrane-bound ILIRs on subpopulations of mononuclear cells or serum levels of soluble IL-1 receptors. It was observed that healthy individuals with the genotype TT in SNP rs2234650.C〉T had a lower percentage of intact CD14＋ monocytes expressing ILIR1 on their surface. The SNP rs4141134-T〉C in ILIR2 has also been associated with the percentage of intact CD3＋ T cells expressing ILIR2. Furthermore, individuals carrying the CC allele of SNP rs4141134.T〉C and the TT allele of SNP rs2071008-T〉G in ILIR2 had a lower density of ILIR2s on the surface of CD14＋ monocytes in lipopolysaccharide （LPS）-stimulated PBMC cultures. In summary, this study demonstrated that IL-1 receptor gene polymorphisms could be one of the factors influencing the expression of membrane-bound IL-1 receptors （ILIR） on immunocompetent cells.
