Abstract:
B cells of people with multiple sclerosis (MS) are more responsive to IFN-γ, corresponding to their brain-homing potential. We studied how a coding single nucleotide polymorphism (SNP) in IFNGR2 (rs9808753) co-operates with Epstein-Barr virus (EBV) infection as MS risk factors to affect the IFN-γ signaling pathway in human B cells. In both cell lines and primary cells, EBV infection positively associated with IFN-γ receptor expression and STAT1 phosphorylation. The IFNGR2 risk SNP selectively promoted downstream signaling via STAT1, particularly in transitional B cells. Altogether, EBV and the IFNGR2 risk SNP independently amplify IFN-γ signaling, potentially driving B cells to enter the MS brain.
摘要:
多发性硬化症(MS)患者的B细胞对IFN-γ更敏感,对应于他们的大脑归巢潜力。我们研究了IFNGR2(rs9808753)中的编码单核苷酸多态性(SNP)如何与EB病毒(EBV)感染作为MS危险因素共同影响人B细胞中IFN-γ信号通路。在细胞系和原代细胞中,EBV感染与IFN-γ受体表达和STAT1磷酸化呈正相关。IFNGR2风险SNP通过STAT1选择性地促进下游信号传导,特别是在过渡B细胞中。总之,EBV和IFNGR2风险SNP独立扩增IFN-γ信号,可能驱动B细胞进入MS大脑。