The DOI matches its Crossref record; 65 of the 65 references it cites were found in a registry or an index.
Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases
Open accessAbstract
Autoreactive memory T lymphocytes are implicated in the pathogenesis of autoimmune diseases. Here we demonstrate that disease-associated autoreactive T cells from patients with type-1 diabetes mellitus or rheumatoid arthritis (RA) are mainly CD4+CCR7−CD45RA−effector memory T cells (T EM cells) with elevated Kv1.3 potassium channel expression. In contrast, T cells with other antigen specificities from these patients, or autoreactive T cells from healthy individuals and disease controls, express low levels of Kv1.3 and are predominantly naïve or central-memory (T CM) cells. In T EM cells, Kv1.3 traffics to the immunological synapse during antigen presentation where it colocalizes with Kvβ2, SAP97, ZIP, p56 lck, and CD4. Although Kv1.3 inhibitors [ShK(L5)-amide (SL5) and PAP1] do not prevent immunological synapse formation, they suppress Ca 2+-signaling, cytokine production, and proliferation of autoantigen-specific T EM cells at pharmacologically relevant concentrations while sparing other classes of T cells. Kv1.3 inhibitors ameliorate pristane-induced arthritis in rats and reduce the incidence of experimental autoimmune diabetes in diabetes-prone (DP-BB/W) rats. Repeated dosing with Kv1.3 inhibitors in rats has not revealed systemic toxicity. Further development of Kv1.3 blockers for autoimmune disease therapy is warranted.
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Cites
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Cited by
Molecular Basis of Calcium Signaling in Lymphocytes: STIM and ORAI
Hogan, P. G., Lewis, R. S., & Rao, A. (2010) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132550 · Cited by 760
Ion channels and transporters in lymphocyte function and immunity
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Role of Ion Channels and Transporters in Cell Migration
Schwab, A., Fabian, A., Hanley, P. J., & Stock, C. (2012) · Physiological Reviews · doi:10.1152/physrev.00018.2011 · Cited by 420
Prediction and Pathogenesis in Type 1 Diabetes
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Self-citationBordon, K. D. C. F., Cologna, C. T., Fornari-Baldo, E. C., Pinheiro-Júnior, E. L., Cerni, F. A., Amorim, F. G., Anjolette, F. A. P., Cordeiro, F. A., Wiezel, G. A., Cardoso, I. A., et al. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01132 · Cited by 303
Metadata
- Authors
- Beeton, C., Wulff, H., Standifer, N. E., Azam, P., Mullen, K. M., Pennington, M. W., Kolski-Andreaco, A., Wei, E., Grino, A., Counts, D. R., Wang, P. H., LeeHealey, C. J., S. Andrews, B., Sankaranarayanan, A., Homerick, D., Roeck, W. W., Tehranzadeh, J., Stanhope, K. L., Zimin, P., Havel, P. J., Griffey, S., Knaus, H.-G., Nepom, G. T., Gutman, G. A., Calabresi, P. A., & Chandy, K. G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-11-14
- Volume
- 103
- Issue
- 46
- Pages
- 17414-17419
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2019310318
- Cited by
- 538
- References
- 65
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- green
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- Beeton, C., Wulff, H., Standifer, N. E., Azam, P., Mullen, K. M., Pennington, M. W., Kolski-Andreaco, A., Wei, E., Grino, A., Counts, D. R., Wang, P. H., LeeHealey, C. J., S. Andrews, B., Sankaranarayanan, A., Homerick, D., Roeck, W. W., Tehranzadeh, J., Stanhope, K. L., Zimin, P., . . . Chandy, K. G. (2006). Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0605136103
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
