Transcriptional signature of human pro-inflammatory T17 cells identifies reduced IL10 gene expression in multiple sclerosis.

We have previously reported the molecular signature of murine pathogenic T17 cells that induce experimental autoimmune encephalomyelitis (EAE) in animals. Here we show that human peripheral blood IFN-γIL-17 (T1/17) and IFN-γIL-17 (T17) CD4 T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to T17 cells, T1/17 cells have gene signatures with marked similarity to mouse pathogenic T17 cells. Assessing 15 representative signature genes in patients with multiple sclerosis, we find that T1/17 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 T17 cells is found in clinically stable vs. active patients. Our results define the molecular signature of human pro-inflammatory T17 cells, which can be used to both identify pathogenic T17 cells and to measure the effect of treatment on T17 cells in human autoimmune diseases.