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Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica
Open accessAbstract
Neuromyelitis optica (NMO) is an inflammatory disease affecting the optic nerve and spinal cord, in which autoantibodies against aquaporin 4 (AQP4) water channel protein probably play a pathogenic role. Here we show that a B-cell subpopulation, exhibiting the CD19 int CD27 high CD38 high CD180 − phenotype, is selectively increased in the peripheral blood of NMO patients and that anti-AQP4 antibodies (AQP4-Abs) are mainly produced by these cells in the blood of these patients. These B cells showed the morphological as well as the phenotypical characteristics of plasmablasts (PB) and were further expanded during NMO relapse. We also demonstrate that interleukin 6 (IL-6), shown to be increased in NMO, enhanced the survival of PB as well as their AQP4-Ab secretion, whereas the blockade of IL-6 receptor (IL-6R) signaling by anti–IL-6R antibody reduced the survival of PB in vitro. These results indicate that the IL-6–dependent B-cell subpopulation is involved in the pathogenesis of NMO, thereby providing a therapeutic strategy for targeting IL-6R signaling.
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Citations
Cited by
IL‐6 in inflammation, immunity, and disease
Tanaka, T., Narazaki, M., & Kishimoto, T. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016295 · Cited by 5,046
Trial of Satralizumab in Neuromyelitis Optica Spectrum Disorder
Yamamura, T., Kleiter, I., Fujihara, K., Palace, J., Greenberg, B., Zakrzewska-Pniewska, B., Patti, F., Tsai, C.-P., Saiz, A., Yamazaki, H., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1901747 · Cited by 664
Self-citationInterleukin-6: designing specific therapeutics for a complex cytokine
Garbers, C., Heink, S., Korn, T., & Rose-John, S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.45 · Cited by 643
Neuromyelitis Optica Study Group (NEMOS), Trebst, C., Jarius, S., Berthele, A., Paul, F., Schippling, S., Wildemann, B., Borisow, N., Kleiter, I., Aktas, O., et al. (2014) · Journal of Neurology · doi:10.1007/s00415-013-7169-7 · Cited by 595
Aquaporins: important but elusive drug targets
Verkman, A. S., Anderson, M. O., & Papadopoulos, M. C. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4226 · Cited by 586
Metadata
- Authors
- Chihara, N., Aranami, T., Sato, W., Miyazaki, Y., Miyake, S., Okamoto, T., Ogawa, M., Toda, T., & Yamamura, T.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2011-02-14
- Volume
- 108
- Issue
- 9
- Pages
- 3701-3706
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2007147688
- Cited by
- 474
- References
- 0
- FWCI
- 18.01
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. https://app.cochat.ai/papers/10.1073/pnas.1017385108
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- Chihara, N., Aranami, T., Sato, W., Miyazaki, Y., Miyake, S., Okamoto, T., Ogawa, M., Toda, T., & Yamamura, T. (2011). Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1017385108
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