Role of transcription factors in regulating human T cell activation and functions
Research area: Molecular Immunology
Group leaders: Silvia Monticelli
Status: In progress
Multiple Sclerosis (MS) is a chronic inflammatory disease with an autoimmune etiology mediated at least in part by CD4+ T lymphocytes producing the pro-inflammatory cytokine Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF). Indeed, GM-CSF was shown to be necessary and sufficient to induce disease in several models of experimental autoimmunity. Levels of GM-CSF were also shown to be increased in patients with MS and to be associated with disease severity. We are investigating mechanisms that regulate the pathogenic potential of T lymphocytes, including the acquired ability to express high levels of GM-CSF. We identified optimal conditions to functionally separate primary human CD4+ T lymphocytes based on their ability to produce high levels of inflammatory cytokines, such as GM-CSF, and we profiled both the transcriptome and miRnome of the cytokine-producing and non-producing populations. We successfully identified candidate genes and miRNAs specifically associated with either the cytokine-producing or non-producing phenotype, and we now initiated studies to understand the biological relevance of such candidates in primary human T lymphocytes from both healthy donors and people with MS.