PhD ceremony Ms. K.A. Smigielska: Involvement of microRNAs in T-cell immunity

PhD ceremony: Ms. K.A. Smigielska

Dissertation: Involvement of microRNAs in T-cell immunity

Promotor(s): prof. J.H.M. van den Berg, prof. A.M.H. Boots

Faculty: Medical Sciences

The molecular cues responsible for the development and function of CD4+ T-cells are still a subject of intensive investigation. MicroRNAs (miRNA), which are small (~22 nt) non-coding RNA molecules, have recently been shown to play an important role in these processes. By binding to their target mRNAs, miRNAs induce mRNA degradation or inhibit translation, and as such regulate the production of cellular proteins. Modulation of cellular miRNAs can cause serious disturbances in the development and functioning of T-cells leading to development of autoimmune diseases in experimental model systems.

In this thesis we set out to investigate the involvement of miRNAs in the functionality of CD4+ T cells of healthy individuals and rheumatoid arthritis (RA) patients. We identified miRNA expression profiles characterizing specific T-cell subsets of healthy donors and RA patients and established novel miRNA signatures specific for naive and memory regulatory T (Treg) cells. In addition, we examined the mechanisms responsible for accumulation of memory Treg cells in the synovial fluid of RA patients. In the second part of the thesis we assessed the influence of T-cell activation on the expression pattern of miRNAs and more specifically studied the function of miR 21 during T cell activation. We showed that T-cell activation introduces dynamic changes to the miRNA profiles, while miR 21 itself provides important signals allowing migration and survival of activated T-cells.

Together, this thesis adds to the knowledge of molecular mechanisms regulating T-cell function in health and disease.