Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis.

We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ+IL-17+ (TH1/17) and IFN-γ-IL-17+ (TH17) CD4+ T cells display distinct transcriptional profiles in...

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Hauptverfasser: Hu, D, Notarbartolo, S, Croonenborghs, T, Patel, B, Cialic, R, Yang, T, Aschenbrenner, D, Andersson, K, Gattorno, M, Pham, M, Kivisakk, P, Pierre, I, Lee, Y, Kiani, K, Bokarewa, M, Tjon, E, Pochet, N, Sallusto, F, Kuchroo, V, Weiner, H
Format: Journal article
Sprache:English
Veröffentlicht: Nature Publishing Group 2017
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author Hu, D
Notarbartolo, S
Croonenborghs, T
Patel, B
Cialic, R
Yang, T
Aschenbrenner, D
Andersson, K
Gattorno, M
Pham, M
Kivisakk, P
Pierre, I
Lee, Y
Kiani, K
Bokarewa, M
Tjon, E
Pochet, N
Sallusto, F
Kuchroo, V
Weiner, H
author_facet Hu, D
Notarbartolo, S
Croonenborghs, T
Patel, B
Cialic, R
Yang, T
Aschenbrenner, D
Andersson, K
Gattorno, M
Pham, M
Kivisakk, P
Pierre, I
Lee, Y
Kiani, K
Bokarewa, M
Tjon, E
Pochet, N
Sallusto, F
Kuchroo, V
Weiner, H
author_sort Hu, D
collection OXFORD
description We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ+IL-17+ (TH1/17) and IFN-γ-IL-17+ (TH17) CD4+ T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH17 cells, TH1/17 cells have gene signatures with marked similarity to mouse pathogenic TH17 cells. Assessing 15 representative signature genes in patients with multiple sclerosis, we find that TH1/17 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 TH17 cells is found in clinically stable vs. active patients. Our results define the molecular signature of human pro-inflammatory TH17 cells, which can be used to both identify pathogenic TH17 cells and to measure the effect of treatment on TH17 cells in human autoimmune diseases.
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spelling oxford-uuid:a0c5a378-6033-468c-803b-407820c79a7a2022-03-27T02:08:01ZTranscriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a0c5a378-6033-468c-803b-407820c79a7aEnglishSymplectic Elements at OxfordNature Publishing Group2017Hu, DNotarbartolo, SCroonenborghs, TPatel, BCialic, RYang, TAschenbrenner, DAndersson, KGattorno, MPham, MKivisakk, PPierre, ILee, YKiani, KBokarewa, MTjon, EPochet, NSallusto, FKuchroo, VWeiner, HWe have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γ+IL-17+ (TH1/17) and IFN-γ-IL-17+ (TH17) CD4+ T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to TH17 cells, TH1/17 cells have gene signatures with marked similarity to mouse pathogenic TH17 cells. Assessing 15 representative signature genes in patients with multiple sclerosis, we find that TH1/17 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 TH17 cells is found in clinically stable vs. active patients. Our results define the molecular signature of human pro-inflammatory TH17 cells, which can be used to both identify pathogenic TH17 cells and to measure the effect of treatment on TH17 cells in human autoimmune diseases.
spellingShingle Hu, D
Notarbartolo, S
Croonenborghs, T
Patel, B
Cialic, R
Yang, T
Aschenbrenner, D
Andersson, K
Gattorno, M
Pham, M
Kivisakk, P
Pierre, I
Lee, Y
Kiani, K
Bokarewa, M
Tjon, E
Pochet, N
Sallusto, F
Kuchroo, V
Weiner, H
Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis.
title Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis.
title_full Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis.
title_fullStr Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis.
title_full_unstemmed Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis.
title_short Transcriptional signature of human pro-inflammatory TH17 cells identifies reduced IL10 gene expression in multiple sclerosis.
title_sort transcriptional signature of human pro inflammatory th17 cells identifies reduced il10 gene expression in multiple sclerosis
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