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

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@article{4148b80062194294bf09f411d069198b,
title = "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 = "Considerable attention has been given to CCR6+ IL-17-secreting CD4+ T cells (Th17) in the pathology of a number of autoimmune diseases including multiple sclerosis (MS). However, other Th subsets also play important pathogenic roles, including those that secrete IFNγ and GM-CSF. CCR6 expression by Th17 cells allows their migration across the choroid plexus into the cerebrospinal fluid (CSF), where they are involved in the early phase of experimental autoimmune encephalomyelitis (EAE), and in MS these cells are elevated in the CSF during relapses and contain high frequencies of autoreactive cells. However, the relatively low frequency of Th17 cells suggests they cannot by themselves account for the high percentage of CCR6+ cells in MS CSF. Here we identify the dominant CCR6+ T cell subsets in both the blood and CSF as non-classic Th1 cells, including many that secrete GM-CSF, a key encephalitogenic cytokine. In addition, we show that Th cells secreting GM-CSF but not IFNγ or IL-17, a subset termed GM-CSF-only-secreting Th cells, also accumulate in the CSF. Importantly, in MS the proportion of IFNγ- and GM-CSF-secreting T cells expressing CCR6 was significantly enriched in the CSF, and was elevated in MS, suggesting these cells play a pathogenic role in this disease.",
keywords = "CCR6, GM-CSF, T cells, Cerebrospinal fluid, Multiple sclerosis, Th1, Th17",
author = "Siobhan Restorick and Lindsay Durant and Seema Kalra and Emma Rathbone and Ghaniah Hassan-Smith and Michael Douglas and John Curnow",
year = "2017",
month = "8",
doi = "10.1016/j.bbi.2017.03.008",
language = "English",
volume = "64",
pages = "71--79",
journal = "Brain, Behaviour, and Immunity",
issn = "0889-1591",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - 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

AU - Restorick, Siobhan

AU - Durant, Lindsay

AU - Kalra, Seema

AU - Rathbone, Emma

AU - Hassan-Smith, Ghaniah

AU - Douglas, Michael

AU - Curnow, John

PY - 2017/8

Y1 - 2017/8

N2 - Considerable attention has been given to CCR6+ IL-17-secreting CD4+ T cells (Th17) in the pathology of a number of autoimmune diseases including multiple sclerosis (MS). However, other Th subsets also play important pathogenic roles, including those that secrete IFNγ and GM-CSF. CCR6 expression by Th17 cells allows their migration across the choroid plexus into the cerebrospinal fluid (CSF), where they are involved in the early phase of experimental autoimmune encephalomyelitis (EAE), and in MS these cells are elevated in the CSF during relapses and contain high frequencies of autoreactive cells. However, the relatively low frequency of Th17 cells suggests they cannot by themselves account for the high percentage of CCR6+ cells in MS CSF. Here we identify the dominant CCR6+ T cell subsets in both the blood and CSF as non-classic Th1 cells, including many that secrete GM-CSF, a key encephalitogenic cytokine. In addition, we show that Th cells secreting GM-CSF but not IFNγ or IL-17, a subset termed GM-CSF-only-secreting Th cells, also accumulate in the CSF. Importantly, in MS the proportion of IFNγ- and GM-CSF-secreting T cells expressing CCR6 was significantly enriched in the CSF, and was elevated in MS, suggesting these cells play a pathogenic role in this disease.

AB - Considerable attention has been given to CCR6+ IL-17-secreting CD4+ T cells (Th17) in the pathology of a number of autoimmune diseases including multiple sclerosis (MS). However, other Th subsets also play important pathogenic roles, including those that secrete IFNγ and GM-CSF. CCR6 expression by Th17 cells allows their migration across the choroid plexus into the cerebrospinal fluid (CSF), where they are involved in the early phase of experimental autoimmune encephalomyelitis (EAE), and in MS these cells are elevated in the CSF during relapses and contain high frequencies of autoreactive cells. However, the relatively low frequency of Th17 cells suggests they cannot by themselves account for the high percentage of CCR6+ cells in MS CSF. Here we identify the dominant CCR6+ T cell subsets in both the blood and CSF as non-classic Th1 cells, including many that secrete GM-CSF, a key encephalitogenic cytokine. In addition, we show that Th cells secreting GM-CSF but not IFNγ or IL-17, a subset termed GM-CSF-only-secreting Th cells, also accumulate in the CSF. Importantly, in MS the proportion of IFNγ- and GM-CSF-secreting T cells expressing CCR6 was significantly enriched in the CSF, and was elevated in MS, suggesting these cells play a pathogenic role in this disease.

KW - CCR6

KW - GM-CSF

KW - T cells

KW - Cerebrospinal fluid

KW - Multiple sclerosis

KW - Th1

KW - Th17

U2 - 10.1016/j.bbi.2017.03.008

DO - 10.1016/j.bbi.2017.03.008

M3 - Article

VL - 64

SP - 71

EP - 79

JO - Brain, Behaviour, and Immunity

JF - Brain, Behaviour, and Immunity

SN - 0889-1591

ER -