Calcineurin/NFAT signalling inhibits myeloid haematopoiesis

EMBO Molecular Medicine

Jan Fric²  Clarice X. F. Lim²  Esther G. L. Koh²  Benjamin Hofmann²  Jinmiao Chen²  Hock Soon Tay²  Siti Aminah Bte Mohammad Isa¹  Alessandra Mortellaro²  Christiane Ruedl¹ 

[1] School of Biological Sciences, Nanyang Technological University, Singapore, Singapore;Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore

关键词: Cyclosporin A;    dendritic cell;    haematopoiesis;    myeloid lineage;    NFAT;   

DOI  :  10.1002/emmm.201100207

来源: Wiley

【 摘 要 】

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.

【 授权许可】

Unknown   
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