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

Abstract 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.