CCR6+ Th cells in the cerebrospinal fluid of persons with multiple sclerosis are dominated by pathogenic non-classic Th1 cells and GM-CSF-only-secreting Th cells

Abstract

HighlightsCCR6+ T helper (Th) cells dominate the cerebrospinal fluid (CSF) in MS.CCR6+ Th17 cells are very rare.The dominant CCR6+ T cell subset secretes IFNγ and is elevated in MS CSF.The encephalitogenic cytokine GM-CSF is also secreted by these cells.GM-CSF-only secreting Th cells, also accumulate in the CSF especially in MS.

Different interleukin‐17‐secreting Toll‐like receptor+ T‐cell subsets are associated with disease activity in multiple sclerosis

“…The presence of GM‐CSF + T‐cell phenotypes have been associated with disease activity in both EAE and MS . This haematopoietic factor should contribute to neuronal damage by inducing recruitment and activation of monocytes into the CNS .…”

“…Although IL‐22 is produced by human Th17 cells, the frequency of a unique subset of IL‐22 producing CD4 + T‐cells (Th22), regardless of IL‐17 release, has been associated with apoptosis of oligodendrocytes, diminished expression of forkhead box protein 3 (FoxP3) and risk of new relapses and number of active brain lesions . Finally, an increased proportion of granulocyte–macrophage colony‐stimulating factor (GM‐CSF)‐secreting T CD4 + cells, some of these co‐expressing IL‐17 or IFN‐ γ , were detected in the CNS of MS patients . Therefore, the ability of some PAMPs to up‐regulate many co‐stimulatory pathways in dendritic cells (DCs) may impact the risk of developing and exacerbating MS.…”

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

“…The only known ligand for the chemokine receptor CCR6, the chemokine CCL20, is constitutively expressed at the BCSFB rather than the BBB implying that CCR6 + Th17 cells access the CNS via the choroid plexuses. In this context it is interesting to note that recognition of myelin oligodendrocyte glycoprotein (MOG) is limited to CCR6 + circulating T cells in multiple sclerosis patients [122] and that CCR6 + T cells are enriched in the CSF of multiple sclerosis patients [115]. On the other hand, CCR6 expression on CSF T cells does not strictly correlate with a Th17 phenotype [115].…”

“…In this context it is interesting to note that recognition of myelin oligodendrocyte glycoprotein (MOG) is limited to CCR6 + circulating T cells in multiple sclerosis patients [122] and that CCR6 + T cells are enriched in the CSF of multiple sclerosis patients [115]. On the other hand, CCR6 expression on CSF T cells does not strictly correlate with a Th17 phenotype [115]. Thus, the CCR6-CCL20 axis may be relevant for the CNS entry of additional CCR6 + T cell subsets, which is supported by the observation that CNS recruitment of CCR6 + FoxP3 + regulatory T cells (T regs ) has also been shown to require CCR6 [163].…”

Gastrointestinal influences in multiple sclerosis: Focus on the role of the microbiome

“…The pathological hallmark of MS is the plaque – an aggregate of T cells, B cells, macrophages, neutrophils, dendritic cells and activated microglia. Although traditionally thought of as a predominantly T‐helper cell type 1‐ (Th1; interferon γ‐producing CD4+ cells) mediated disease, there is increasing evidence that Th17 cells (producing predominantly interleukin [IL]‐17), as well as a novel granulocyte‐macrophage colony‐stimulating factor‐producing T cell, are critical in both MS and the animal model, experimental autoimmune encephalomyelitis (EAE) . MS results from an imbalance between inflammatory cells (such as Th1/Th17) and regulatory mechanisms, including regulatory T cells (Treg; producing IL‐10).…”