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

Dan Hu, Samuele Notarbartolo, Tom Croonenborghs, Bonny Patel, Ron Cialic, Tun-Hsiang Yang, Dominik Aschenbrenner, Karin M Andersson, Marco Gattorno, Minh Pham, Pia Kivisakk, Isabelle V Pierre, Youjin Lee, Karun Kiani, Maria Bokarewa, Emily Tjon, Nathalie Pochet, Federica Sallusto, Vijay K Kuchroo, Howard L Weiner

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1600
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - Nov 17 2017

Keywords

  • Journal Article

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