Impact of coding risk variant IFNGR2 on the B cell-intrinsic IFN-γ signaling pathway in multiple sclerosis.
Laurens BogersJasper RipLiza RijversJamie van LangelaarSteven C KoetzierKirsten L KuiperVeronique MeerdinkAnnet F Wierenga-WolfMarie-José MeliefAna M MarquesJoost SmoldersMarvin M van LuijnPublished in: Journal of autoimmunity (2024)
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.
Keyphrases
- epstein barr virus
- multiple sclerosis
- diffuse large b cell lymphoma
- white matter
- dendritic cells
- signaling pathway
- immune response
- mass spectrometry
- induced apoptosis
- genome wide
- risk factors
- ms ms
- endothelial cells
- pi k akt
- resting state
- cell proliferation
- epithelial mesenchymal transition
- functional connectivity
- gene expression
- oxidative stress
- genetic diversity
- human health
- risk assessment
- induced pluripotent stem cells
- cancer therapy
- pluripotent stem cells