Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Uschnig, C.
Foxp3+ regulatory T cell induction by murine and human Dendritic cells
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2015. pp.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Strobl Herbert
- Altmetrics:
- Abstract:
- Dendritic cells (DCs) are specialized antigen-presenting cells composed of phenotypically, functionally, and developmentally diverse subsets. DCs are critical for adaptive immunity, as well as for the induction and maintenance of immune tolerance. One way by which DCs regulate tolerance is through the induction of regulatory T cells (Treg), which are essential for regulating self-tolerance and preventing autoimmune disease. Here, we generated induced-tolerogenic (it) DCs via short-term exposure to the mTOR inhibitor rapamycin and transforming growth factor beta (TGFb). Given the diversity of different DC subsets, we assessed the tolerogenic potential of five different murine subsets to explore the therapeutic potential of it-DC therapy in an allergy model, i.e. allergic asthma. In addition, we applied the same stimuli to five different human subsets in order to assess their potential to induce Tregs in vitro. Investigation of murine splenic DC subsets revealed: (1) that CD11c+ it-DC subsets (CD4+, CD8a+, CD11b+, triple negative (TN), pDC) were able to convert antigen-specific naïve OT-II T cells into Foxp3+ CD25hi Tregs, compared to immunogenic DCs; (2) that adoptive transfer of antigen-pulsed it-DCs induced Foxp3+ Tregs in vivo; and (3) that the therapeutic injection of one of the it-DC subsets induced tolerance in an murine model of allergic asthma. In addition to murine DCs, we investigated four human blood DC subsets (CD141+, CD16+, CD1c+, pDC), and monocyte-derived DCs. In humans, CD16+ it-DCs and monocyte-derived it-DCs preferentially induced the conversion of naïve T cells into the Tregs. In light of these novel findings, we proposed it-DCs as a potential novel cellular therapeutic strategy for the treatment of T cell-mediated allergic disorders, such as allergic asthma.