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Title: | Differential Runx3, Eomes, and T-bet expression subdivides MS-associated CD4+ T cells with brain-homing capacity | Authors: | 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. |
Issue Date: | 2023 | Publisher: | WILEY | Source: | EUROPEAN JOURNAL OF IMMUNOLOGY, | Status: | Early view | 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. | 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. m.vanluijn@erasmusmc.nl |
Keywords: | Pathogenic CD4(+) T cells;Th17.1;CD4(+)CD28(-);Runx3;Eomes;T-bet;Multiple sclerosis | Document URI: | http://hdl.handle.net/1942/41942 | ISSN: | 0014-2980 | e-ISSN: | 1521-4141 | DOI: | 10.1002/eji.202350544 | ISI #: | 001115674600001 | 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. | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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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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