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http://hdl.handle.net/1942/41942
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DC Field | Value | Language |
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dc.contributor.author | HOEKS, Cindy | - |
dc.contributor.author | van Puijfelik, Fabienne | - |
dc.contributor.author | Koetzier, Steven C. | - |
dc.contributor.author | Rip, Jasper | - |
dc.contributor.author | Corsten, Cato E. A. | - |
dc.contributor.author | Wierenga-Wolf, Annet F. | - |
dc.contributor.author | Melief, Marie-Jose | - |
dc.contributor.author | STINISSEN, Piet | - |
dc.contributor.author | Smolders, Joost | - |
dc.contributor.author | HELLINGS, Niels | - |
dc.contributor.author | BROUX, Bieke | - |
dc.contributor.author | van Luijn, Marvin M. | - |
dc.date.accessioned | 2023-12-15T10:33:36Z | - |
dc.date.available | 2023-12-15T10:33:36Z | - |
dc.date.issued | 2023 | - |
dc.date.submitted | 2023-12-15T10:09:35Z | - |
dc.identifier.citation | EUROPEAN JOURNAL OF IMMUNOLOGY, | - |
dc.identifier.uri | http://hdl.handle.net/1942/41942 | - |
dc.description.abstract | Multiple sclerosis (MS) is a common and devastating chronic inflammatory disease of the CNS. CD4(+) T cells are assumed to be the first to cross the blood-central nervous system (CNS) barrier and trigger local inflammation. Here, we explored how pathogenicity-associated effector programs define CD4(+) T cell subsets with brain-homing ability in MS. Runx3- and Eomes-, but not T-bet-expressing CD4(+) memory cells were diminished in the blood of MS patients. This decline reversed following natalizumab treatment and was supported by a Runx3(+)Eomes(+)T-bet- enrichment in cerebrospinal fluid samples of treatment-naive MS patients. This transcription factor profile was associated with high granzyme K (GZMK) and CCR5 levels and was most prominent in Th17.1 cells (CCR6(+)CXCR3(+)CCR4(-/dim)). Previously published CD28- CD4 T cells were characterized by a Runx3(+)Eomes(-)T-bet(+) phenotype that coincided with intermediate CCR5 and a higher granzyme B (GZMB) and perforin expression, indicating the presence of two separate subsets. Under steady-state conditions, granzyme K-high Th17.1 cells spontaneously passed the blood-brain barrier in vitro. This was only found for other subsets including CD28(-) cells when using inflamed barriers. Altogether, CD4(+ )T cells contain small fractions with separate pathogenic features, of which Th17.1 seems to breach the blood-brain barrier as a possible early event in MS. | - |
dc.description.sponsorship | The hCMEC/D3 cell line was provided by Tebubio (Le Perray-en-Yvelines, France). This study was funded by the Dutch MS Research Foundation (19-1057 MS, 19-1075 MS, and 20-490f MS) and the Dutch Research Council (ZonMw-Vidi grant 09150171910036). | - |
dc.language.iso | en | - |
dc.publisher | WILEY | - |
dc.rights | 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | - |
dc.subject.other | Pathogenic CD4(+) T cells | - |
dc.subject.other | Th17.1 | - |
dc.subject.other | CD4(+)CD28(-) | - |
dc.subject.other | Runx3 | - |
dc.subject.other | Eomes | - |
dc.subject.other | T-bet | - |
dc.subject.other | Multiple sclerosis | - |
dc.title | Differential Runx3, Eomes, and T-bet expression subdivides MS-associated CD4+ T cells with brain-homing capacity | - |
dc.type | Journal Contribution | - |
local.format.pages | 15 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | van Luijn, MM (corresponding author), Erasmus MC, MS Ctr ErasMS, Univ Med Ctr Rotterdam, Dept Immunol, Wytemaweg 80,Room Nb 1142a, NL-3015 CN Rotterdam, Netherlands. | - |
dc.description.notes | m.vanluijn@erasmusmc.nl | - |
local.publisher.place | 111 RIVER ST, HOBOKEN 07030-5774, NJ USA | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
local.bibliographicCitation.status | Early view | - |
dc.identifier.doi | 10.1002/eji.202350544 | - |
dc.identifier.pmid | 38009648 | - |
dc.identifier.isi | 001115674600001 | - |
dc.contributor.orcid | Smolders, Joost/0000-0001-9766-8661; Rip, Jasper/0000-0001-5780-9271; | - |
dc.contributor.orcid | Koetzier, Steven C./0000-0002-7000-9321; van Puijfelik, | - |
dc.contributor.orcid | Fabienne/0000-0002-7257-4455 | - |
local.provider.type | wosris | - |
local.description.affiliation | [Hoeks, Cindy; Stinissen, Piet; Hellings, Niels; Broux, Bieke] Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, Hasselt, Belgium. | - |
local.description.affiliation | [Hoeks, Cindy; Stinissen, Piet; Hellings, Niels; Broux, Bieke] Univ MS Ctr UMSC, Hasselt, Belgium. | - |
local.description.affiliation | [van Puijfelik, Fabienne; Koetzier, Steven C.; Rip, Jasper; Wierenga-Wolf, Annet F.; Melief, Marie-Jose; Smolders, Joost; van Luijn, Marvin M.] Erasmus MC, MS Ctr ErasMS, Univ Med Ctr Rotterdam, Dept Immunol, Wytemaweg 80,Room Nb 1142a, NL-3015 CN Rotterdam, Netherlands. | - |
local.description.affiliation | [Corsten, Cato E. A.; Smolders, Joost] Erasmus MC, MS Ctr ErasMS, Dept Neurol, Univ Med Ctr Rotterdam, Rotterdam, Netherlands. | - |
local.description.affiliation | [Smolders, Joost] Netherlands Inst Neurosci, Neuroimmunol Res Grp, Amsterdam, Netherlands. | - |
local.uhasselt.international | yes | - |
item.fullcitation | HOEKS, Cindy; van Puijfelik, Fabienne; Koetzier, Steven C.; Rip, Jasper; Corsten, Cato E. A.; Wierenga-Wolf, Annet F.; Melief, Marie-Jose; STINISSEN, Piet; Smolders, Joost; HELLINGS, Niels; BROUX, Bieke & van Luijn, Marvin M. (2023) Differential Runx3, Eomes, and T-bet expression subdivides MS-associated CD4+ T cells with brain-homing capacity. In: EUROPEAN JOURNAL OF IMMUNOLOGY,. | - |
item.contributor | HOEKS, Cindy | - |
item.contributor | van Puijfelik, Fabienne | - |
item.contributor | Koetzier, Steven C. | - |
item.contributor | Rip, Jasper | - |
item.contributor | Corsten, Cato E. A. | - |
item.contributor | Wierenga-Wolf, Annet F. | - |
item.contributor | Melief, Marie-Jose | - |
item.contributor | STINISSEN, Piet | - |
item.contributor | Smolders, Joost | - |
item.contributor | HELLINGS, Niels | - |
item.contributor | BROUX, Bieke | - |
item.contributor | van Luijn, Marvin M. | - |
item.accessRights | Open Access | - |
item.fulltext | With Fulltext | - |
crisitem.journal.issn | 0014-2980 | - |
crisitem.journal.eissn | 1521-4141 | - |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
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Eur J Immunol - 2023 - Hoeks - Differential Runx3 Eomes and T‐bet expression subdivides MS‐associated CD4 T cells with.pdf | Early view | 3.7 MB | Adobe PDF | View/Open |
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