T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention

CD4+ T helper 17 (Th17) cells are key regulators of multiple sclerosis disease activity, but functionally heterogeneous. Van Langelaar et al. report that Th1-like Th17 (Th17.1) cells are associated with rapid disease onset and effective natalizumab treatment responses in patients with multiple scler...

Full description

Saved in:
Bibliographic Details
Published in:Brain (London, England : 1878) England : 1878), 2018-05, Vol.141 (5), p.1334-1349
Main Authors: van Langelaar, Jamie, van der Vuurst de Vries, Roos M, Janssen, Malou, Wierenga-Wolf, Annet F, Spilt, Isis M, Siepman, Theodora A, Dankers, Wendy, Verjans, Georges M G M, de Vries, Helga E, Lubberts, Erik, Hintzen, Rogier Q, van Luijn, Marvin M
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:CD4+ T helper 17 (Th17) cells are key regulators of multiple sclerosis disease activity, but functionally heterogeneous. Van Langelaar et al. report that Th1-like Th17 (Th17.1) cells are associated with rapid disease onset and effective natalizumab treatment responses in patients with multiple sclerosis. The findings support early targeting of Th17.1 cells. Abstract Interleukin-17-expressing CD4+ T helper 17 (Th17) cells are considered as critical regulators of multiple sclerosis disease activity. However, depending on the species and pro-inflammatory milieu, Th17 cells are functionally heterogeneous, consisting of subpopulations that differentially produce interleukin-17, interferon-gamma and granulocyte macrophage colony-stimulating factor. In the current study, we studied distinct effector phenotypes of human Th17 cells and their correlation with disease activity in multiple sclerosis patients. T helper memory populations single- and double-positive for C-C chemokine receptor 6 (CCR6) and CXC chemokine receptor 3 (CXCR3) were functionally assessed in blood and/or cerebrospinal fluid from a total of 59 patients with clinically isolated syndrome, 35 untreated patients and 24 natalizumab-treated patients with relapsing-remitting multiple sclerosis, and nine patients with end-stage multiple sclerosis. Within the clinically isolated syndrome group, 23 patients had a second attack within 1 year and 26 patients did not experience subsequent attacks during a follow-up of >5 years. Low frequencies of T helper 1 (Th1)-like Th17 (CCR6+CXCR3+), and not Th17 (CCR6+CXCR3−) effector memory populations in blood strongly associated with a rapid diagnosis of clinically definite multiple sclerosis. In cerebrospinal fluid of clinically isolated syndrome and relapsing-remitting multiple sclerosis patients, Th1-like Th17 effector memory cells were abundant and showed increased production of interferon-gamma and granulocyte macrophage colony-stimulating factor compared to paired CCR6+ and CCR6−CD8+ T cell populations and their blood equivalents after short-term culturing. Their local enrichment was confirmed ex vivo using cerebrospinal fluid and brain single-cell suspensions. Across all pro-inflammatory T helper cells analysed in relapsing-remitting multiple sclerosis blood, Th1-like Th17 subpopulation T helper 17.1 (Th17.1; CCR6+CXCR3+CCR4−) expressed the highest very late antigen-4 levels and selectively accumulated in natalizumab-treated patients who remained free of clini
ISSN:0006-8950
1460-2156
DOI:10.1093/brain/awy069