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Title: Calcineurin/NFAT signalling inhibits myeloid haematopoiesis
Authors: Fric, Jan
Hofmann, Benjamin
Chen, Jinmiao
Tay, Hock Soon
Siti Aminah Mohammad Isa
Mortellaro, Alessandra
Ruedl, Christiane
Ricciardi-Castagnoli, Paola
Lim, Clarice X. F.
Koh, Esther G. L.
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2012
Source: Fric, J., Lim, C. X. F., Koh, E. G. L., Hofmann, B., Chen, J., Tay, H. S., Siti, A. M. I., Mortellaro, A., Ruedl, C.,& Ricciardi-Castagnoli, P. (2012). Calcineurin/NFAT signalling inhibits myeloid haematopoiesis. EMBO Molecular Medicine, 4(4), 269-282.
Series/Report no.: EMBO molecular medicine
Abstract: Nuclear factor of activated T cells (NFAT) comprises a family of transcription factors that regulate T cell development, activation and differentiation. NFAT signalling can also mediate granulocyte and dendritic cell (DC) activation, but it is unknown whether NFAT influences their development from progenitors. Here, we report a novel role for calcineurin/NFAT signalling as a negative regulator of myeloid haematopoiesis. Reconstituting lethally irradiated mice with haematopoietic stem cells expressing an NFAT-inhibitory peptide resulted in enhanced development of the myeloid compartment. Culturing bone marrow cells in media supplemented with Flt3-L in the presence of the calcineurin/NFAT inhibitor Cyclosporin A increased numbers of differentiated DC. Global gene expression analysis of untreated DC and NFAT-inhibited DC revealed differential expression of transcripts that regulate cell cycle and apoptosis. In conclusion, these results provide evidence that calcineurin/NFAT signalling negatively regulates myeloid lineage development. The finding that inhibition of NFAT enhances myeloid development provides a novel insight into understanding how the treatment with drugs targeting calcineurin/NFAT signalling influence the homeostasis of the innate immune system.
ISSN: 1757-4676
DOI: 10.1002/emmm.201100207
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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