Impact of coding risk variant IFNGR2 on the B cell-intrinsic IFN-γ signaling pathway in multiple sclerosis

Laurens Bogers; Jasper Rip; Liza Rijvers; Jamie van Langelaar; Steven C Koetzier; Kirsten L Kuiper; Veronique Meerdink; Annet F Wierenga-Wolf; Marie-José Melief; Ana M Marques; Joost Smolders; Marvin M van Luijn

doi:10.1016/j.jaut.2024.103279

Impact of coding risk variant IFNGR2 on the B cell-intrinsic IFN-γ signaling pathway in multiple sclerosis

Laurens Bogers, Jasper Rip, Liza Rijvers, Jamie van Langelaar, Steven C Koetzier, Kirsten L Kuiper, Veronique Meerdink, Annet F Wierenga-Wolf, Marie-José Melief, Ana M Marques, Joost Smolders, Marvin M van Luijn^*

^*Corresponding author for this work

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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.

Original language	English
Article number	103279
Pages (from-to)	103279
Journal	Journal of Autoimmunity
Volume	148
DOIs	https://doi.org/10.1016/j.jaut.2024.103279
Publication status	Published - Sept 2024

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© 2024 The Authors

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1-s2.0-S0896841124001136-mainFinal published version, 3.32 MBLicence: CC BY

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Bogers, L., Rip, J., Rijvers, L., van Langelaar, J., Koetzier, S. C., Kuiper, K. L., Meerdink, V., Wierenga-Wolf, A. F., Melief, M.-J., Marques, A. M., Smolders, J., & van Luijn, M. M. (2024). Impact of coding risk variant IFNGR2 on the B cell-intrinsic IFN-γ signaling pathway in multiple sclerosis. Journal of Autoimmunity, 148, 103279. Article 103279. https://doi.org/10.1016/j.jaut.2024.103279

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title = "Impact of coding risk variant IFNGR2 on the B cell-intrinsic IFN-γ signaling pathway in multiple sclerosis",

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.",

author = "Laurens Bogers and Jasper Rip and Liza Rijvers and {van Langelaar}, Jamie and Koetzier, {Steven C} and Kuiper, {Kirsten L} and Veronique Meerdink and Wierenga-Wolf, {Annet F} and Marie-Jos{\'e} Melief and Marques, {Ana M} and Joost Smolders and {van Luijn}, {Marvin M}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = sep,

doi = "10.1016/j.jaut.2024.103279",

language = "English",

volume = "148",

pages = "103279",

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Bogers, L , Rip, J, Rijvers, L, van Langelaar, J, Koetzier, SC, Kuiper, KL, Meerdink, V, Wierenga-Wolf, AF , Melief, M-J , Marques, AM , Smolders, J & van Luijn, MM 2024, 'Impact of coding risk variant IFNGR2 on the B cell-intrinsic IFN-γ signaling pathway in multiple sclerosis', Journal of Autoimmunity, vol. 148, 103279, pp. 103279. https://doi.org/10.1016/j.jaut.2024.103279

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T1 - Impact of coding risk variant IFNGR2 on the B cell-intrinsic IFN-γ signaling pathway in multiple sclerosis

AU - Bogers, Laurens

AU - Rip, Jasper

AU - Rijvers, Liza

AU - van Langelaar, Jamie

AU - Koetzier, Steven C

AU - Kuiper, Kirsten L

AU - Meerdink, Veronique

AU - Wierenga-Wolf, Annet F

AU - Melief, Marie-José

AU - Marques, Ana M

AU - Smolders, Joost

AU - van Luijn, Marvin M

PY - 2024/9

Y1 - 2024/9

N2 - 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.

AB - 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.

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JO - Journal of Autoimmunity

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Impact of coding risk variant IFNGR2 on the B cell-intrinsic IFN-γ signaling pathway in multiple sclerosis

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