ANTIGEN SPECIFICITY ENHANCES DISEASE CONTROL BY TREGS IN VITILIGO

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dc.contributor.authorMukhatayev, Zhussipbek
dc.contributor.authorDellacecca, Emilia R.
dc.contributor.authorCosgrove, Cormac
dc.contributor.authorShivde, Rohan
dc.contributor.authorJaishankar, Dinesh
dc.contributor.authorPontarolo-Maag, Katherine
dc.contributor.authorEby, Jonathan M.
dc.contributor.authorHenning, Steven W.
dc.contributor.authorOstapchuk, Yekaterina O.
dc.contributor.authorCedercreutz, Kettil
dc.contributor.authorIssanov, Alpamys
dc.contributor.authorMehrotra, Shikhar
dc.contributor.authorOverbeck, Andreas
dc.contributor.authorJunghans, Richard P.
dc.contributor.authorLeventhal, Joseph R.
dc.contributor.authorLe Poole, I. Caroline
dc.date.accessioned2021-02-01T09:43:18Z
dc.date.available2021-02-01T09:43:18Z
dc.date.issued2020-12-01
dc.description.abstractVitiligo is an autoimmune skin disease characterized by melanocyte destruction. Regulatory T cells (Tregs) are greatly reduced in vitiligo skin, and replenishing peripheral skin Tregs can provide protection against depigmentation. Ganglioside D3 (GD3) is overexpressed by perilesional epidermal cells, including melanocytes, which prompted us to generate GD3-reactive chimeric antigen receptor (CAR) Tregs to treat vitiligo. Mice received either untransduced Tregs or GD3-specific Tregs to test the hypothesis that antigen specificity contributes to reduced autoimmune reactivity in vitro and in vivo. CAR Tregs displayed increased IL-10 secretion in response to antigen, provided superior control of cytotoxicity towards melanocytes, and supported a significant delay in depigmentation compared to untransduced Tregs and vehicle control recipients in a TCR transgenic mouse model of spontaneous vitiligo. The latter findings were associated with a greater abundance of Tregs and melanocytes in treated mice versus both control groups. Our data support the concept that antigen-specific Tregs can be prepared, used, and stored for long-term control of progressive depigmentation.en_US
dc.identifier.citationMukhatayev, Z., Dellacecca, E. R., Cosgrove, C., Shivde, R., Jaishankar, D., Pontarolo-Maag, K., Eby, J. M., Henning, S. W., Ostapchuk, Y. O., Cedercreutz, K., Issanov, A., Mehrotra, S., Overbeck, A., Junghans, R. P., Leventhal, J. R., & Le Poole, I. C. (2020). Antigen Specificity Enhances Disease Control by Tregs in Vitiligo. Frontiers in Immunology, 11. https://doi.org/10.3389/fimmu.2020.581433en_US
dc.identifier.issn1664-3224
dc.identifier.urihttps://doi.org/10.3389/fimmu.2020.581433
dc.identifier.urihttps://www.frontiersin.org/articles/10.3389/fimmu.2020.581433/full
dc.identifier.urihttp://nur.nu.edu.kz/handle/123456789/5265
dc.language.isoenen_US
dc.publisherFrontiers Mediaen_US
dc.relation.ispartofseriesFrontiers in Immunology;11
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subjectvitiligoen_US
dc.subjectregulatory T cellsen_US
dc.subjectchimeric antigen receptor T cellsen_US
dc.subjectganglioside D3en_US
dc.subjectantigen-specific Tregen_US
dc.subjectautoimmune diseasesen_US
dc.subjectResearch Subject Categories::MEDICINEen_US
dc.titleANTIGEN SPECIFICITY ENHANCES DISEASE CONTROL BY TREGS IN VITILIGOen_US
dc.typeArticleen_US
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