TY  - JOUR
A1  - Baur, Johannes
A1  - Otto, Christoph
A1  - Steger, Ulrich
A1  - Klein-Hessling, Stefan
A1  - Muhammad, Khalid
A1  - Pusch, Tobias
A1  - Murti, Krisna
A1  - Wismer, Rhoda
A1  - Germer, Christoph-Thomas
A1  - Klein, Ingo
A1  - Müller, Nora
A1  - Serfling, Edgar
A1  - Avots, Andris
T1  - The transcription factor NFaTc1 supports the rejection of heterotopic heart allografts
T2  - Frontiers in Immunology
N2  - 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.
KW  - NFATc1
KW  - transplantation
KW  - heterologous
KW  - CD8+ T cells
KW  - ChIPseq
KW  - metabolism
Y1  - 2018
UR  - https://opus.bibliothek.uni-wuerzburg.de/opus4-wuerzburg/frontdoor/index/index/docId/22153
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-221530
VL  - 9
ER  -