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.
Highlights
We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals
TH17 cells are a subset of interleukin-17 (IL-17)-secreting Thelper (TH) cells implicated in the pathogenesis of multiple sclerosis (MS), rheumatoid arthritis, juvenile idiopathic arthritis (JIA), and psoriasis[1,2], whose differentiation is regulated by the transcription factor RAR-related orphan nuclear receptor gamma (RORγt)[3]
When we compare clinically active vs. stable patients, we find that stable patients have higher IL10 expression in TH17 cells, whereas active patients have higher expression of STAT3 in IFNγ–/IL-17– CD4+ T cells
Summary
We have previously reported the molecular signature of murine pathogenic TH17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. 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. Ann Romney Center for Neurologic Diseases and Evergrande Center for Immunologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA. 3 Program in Translational NeuroPsychiatric Genomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA. Murine TH17 cells are pathogenic or nonpathogenic based on their ability to induce experimental autoimmune encephalomyelitis (EAE)[12]; pathogenic TH17 cells express higher levels of IFN-γ while non-pathogenic TH17 cells produce IL-10 with IL-1713
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