Refine
Has Fulltext
- yes (19)
Is part of the Bibliography
- yes (19)
Year of publication
Document Type
- Journal article (11)
- Doctoral Thesis (7)
- Habilitation (1)
Keywords
- transplantation (19) (remove)
Institute
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (6)
- Medizinische Klinik und Poliklinik II (4)
- Neurologische Klinik und Poliklinik (3)
- Kinderklinik und Poliklinik (2)
- Theodor-Boveri-Institut für Biowissenschaften (2)
- Abteilung für Funktionswerkstoffe der Medizin und der Zahnheilkunde (1)
- Comprehensive Cancer Center Mainfranken (1)
- Institut für Hygiene und Mikrobiologie (1)
- Institut für Medizinische Strahlenkunde und Zellforschung (1)
- Institut für Virologie und Immunbiologie (1)
The immune suppressants cyclosporin A (CsA) and tacrolimus (FK506) are used worldwide in transplantation medicine to suppress graft rejection. Both CsA and FK506 inhibit the phosphatase calcineurin (CN) whose activity controls the immune receptor-mediated activation of lymphocytes. Downstream targets of CN in lymphocytes are the nuclear factors of activated T cells (NFATs). We show here that the activity of NFATc1, the most prominent NFAT factor in activated lymphocytes supports the acute rejection of heterotopic heart allografts. While ablation of NFATc1 in T cells prevented graft rejection, ectopic expression of inducible NFATc1/αA isoform led to rejection of heart allografts in recipient mice. Acceptance of transplanted hearts in mice bearing NFATc1-deficient T cells was accompanied by a reduction in number and cytotoxicity of graft infiltrating cells. In CD8\(^+\) T cells, NFATc1 controls numerous intracellular signaling pathways that lead to the metabolic switch to aerobic glycolysis and the expression of numerous lymphokines, chemokines, and their receptors, including Cxcr3 that supports the rejection of allogeneic heart transplants. These findings favors NFATc1 as a molecular target for the development of new strategies to control the cytotoxicity of T cells upon organ transplantation.