Unravelling the transcriptional circuit regulating IL-10 production in human Th17 cells
Research area: Cellular Immunology
Group leaders: Federica Sallusto
Status: In progress
IL-17 producing CD4+ cells (Th17) are a subset of effector T helper cells known to play an important role in host defense against fungi and extracellular bacteria but also involved in tissue inflammation and autoimmune diseases, such as multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. The function of Th17 cells depends critically on the range of cytokines produced and on the balance between pro- and anti-inflammatory cytokines. Autoreactive Th17 cells producing IFN-γ and GM-CSF are pathogenic in a mouse model of EAE, while Th17 cells producing IL-10 are not. We have recently shown that C. albicans-specific human Th17 cells produce IL-17 and IFN-γ, while S. aureus-specific human Th17 cells produce IL-17 and, after restimulation, IL-10. While the ontology of the two different Th17 subsets has been clarified, it still remains elusive what is the transcriptional circuit that regulates the expression of the immunoregulatory molecule IL-10. Using a combination of transcriptional profiling and epigenetic approach, we identified the transcription factor c-MAF as a candidate for the regulation of IL-10 production in human Th17 cells, thus potentially representing a discriminant factor between pathogenic and non pathogenic Th17 cells.