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Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis
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Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis
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Journal Article
Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis
2017
Overview
We have previously reported the molecular signature of murine pathogenic T
H
17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ
+
IL-17
+
(T
H
1/17) and IFN-γ
−
IL-17
+
(T
H
17) CD4
+
T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to T
H
17 cells, T
H
1/17 cells have gene signatures with marked similarity to mouse pathogenic T
H
17 cells. Assessing 15 representative signature genes in patients with multiple sclerosis, we find that T
H
1/17 cells have elevated expression of
CXCR3
and reduced expression of
IFNG
,
CCL3
,
CLL4
,
GZMB
, and
IL10
compared to healthy controls. Moreover, higher expression of
IL10
in T
H
17 cells is found in clinically stable vs. active patients. Our results define the molecular signature of human pro-inflammatory T
H
17 cells, which can be used to both identify pathogenic T
H
17 cells and to measure the effect of treatment on T
H
17 cells in human autoimmune diseases.
CD4
+
T cells secreting interleukin-17 (T
H
17) have diverse functions in modulating autoimmune diseases. Here the authors show via transcriptome analyses that a subset of human T
H
17 co-expressing interferon-γ (T
H
1/17) has a molecular signature similar to “pathogenic” mouse T
H
17 but distinct from “non-pathogenic” mouse T
H
17.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
