The Transcription Factor nFaTc1 supports the rejection of heterotopic heart allografts

Murti, Krisna and Baur, Johannes and Otto, Christoph and Steger, Ulrich and Hessling, Stefan Klein and Muhammad, Khalid and Pusch, Tobias and Wismer, Rhoda and Germer, Christoph Thomas and Klein, Ingo and Muller, Nora and Serfling, Edgar and Avots, Andris (2018) The Transcription Factor nFaTc1 supports the rejection of heterotopic heart allografts. Frontiers in Immunology, 9. pp. 1-12. ISSN 16643224

Text The transcription factor NFATc1 supports the rejection of heterotopic heart allografts.pdf Download (12MB)

Abstract

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-defcient T cells was accompanied by a reduction in number and cytotoxicity of graft infltrating 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 fndings favors NFATc1 as a molecular target for the development of new strategies to control the cytotoxicity of T cells upon organ transplantation. Keywords: nFaTc1, transplantation, heterologous, cD8+ T cells, chiPseq, metabolism

Item Type:	Article
Subjects:	R Medicine > R Medicine (General) > R5-920 Medicine (General)
Divisions:	04-Faculty of Medicine > 11718-Pathology Anatomy (Sp
Depositing User:	dr., Ph.D. Krisna Murti
Date Deposited:	11 May 2023 15:23
Last Modified:	11 May 2023 15:23
URI:	http://repository.unsri.ac.id/id/eprint/101490

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