Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>microRNAs (miRNAs) are posttranscriptional regulators of the proteome. We have identified CD28-responsive miRNAs in human CD4+ T cells. Among others, the miR-17-92 cluster was of particular interest because abnormal miR-17 levels have been reported in peripheral blood mononuclear cells from patients with multiple sclerosis. When activated with low CD28-costimulation the miR-17-92 cluster was necessary to drive maximal proliferation in conventional mouse CD4+ T cells (Tconv) in vitro. However, the miR-17-92 cluster was largely dispensable for total T cell numbers in secondary lymphoid tissues and for antigen-response in vivo. Since FoxP3+ regulatory T cells (Treg) are strongly co-stimulation dependent we deleted the miR-17-92 cluster specifically in Treg. Preliminary data suggest that as for Tconv the miR-17-92 cluster was dispensable for Treg numbers and function under homeostatic conditions, even in aging mice. By contrast, mice with miR-17-92-deficient Treg develop much more severe experimental autoimmune encephalitis than control mice. Preliminary results suggest that miR-17-92-deficient Treg numbers are significantly reduced in the spinal cord while antigen-specific effector cells are present in normal numbers. We are currently investigating how miR-17-92 mediates this crucial function. Our results demonstrate that miRNAs are critical for optimal T cell co-stimulation via CD28. The miR-17-92 cluster is essential for Treg function under inflammatory conditions in vivo.</jats:p>