Transcriptional signature of human pro-inflammatory T(H)17 cells identifies reduced IL10 gene expression in multiple sclerosis

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.