Research interests

We investigate gene expression in CD4 T cells, which directs processes of activation, differentiation or effector function as well as inactivation and tolerance induction. Our ongoing projects study the regulation of mRNA transcription, of mRNA stability, RNA processing, oligouridylation of RNA and posttranscriptional repression.

CD4 helper T cells shape the immune response and permit effective clearance of pathogens. Besides their crucial function in immunity, they also play negative roles. In fact, recognition of self-antigens by CD4 T cells is causally related to the development of many autoimmune diseases and unbalanced activation of CD4 T cells through environmental antigens trigger allergies.
 
Antigen-induced T cell receptor (TCR) signal transduction not only stimulates cell activation and proliferation, but also triggers CD4 T cells to differentiate. TCR-signaling in a specific cellular context and humoral milieu can convert naïve CD4 T cells into Th1, Th2, Th17, follicular helper T cells (Tfh) or regulatory T cells (Treg cells). The Th1, Th2, Tfh and Th17 effector T cells secrete cytokines upon recognition of antigen and stimulate specific immune responses and inflammation or provide critical help to B cells for antibody production. In contrast, regulatory T cells suppress activation of bystander T cells and prevent responses. These cells protect us from fatal autoimmunity, but may also help tumor cells to escape immune surveillance.
 
Within the programs of CD4 T cell activation, differentiation and tolerance we focus on the regulation through transcription factors and miRNAs as well as proteins that control the half-life of mRNAs. These are trans-acting factors that recognize cis-regulatory sequences. For example, transcription factors bind to specific sequences in promoters and enhancers of the DNA and miRNAs or RNA-binding proteins bind to specific sequences in the 3’UTR of mRNAs. These systems therefore may have co-evolved to complement each other in the concerted up- and downregulation of target genes to bring about rapid and effective changes in the gene expression program that are necessary to elicit a specific cellular response.

Knowing the molecular mechanisms that drive or inhibit specific immune responses will provide the basis for future therapeutic intervention in pathogenic changes with a major contribution from the immune system.

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