Calcineurin/NFAT signalling inhibits myeloid haematopoiesis
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 fro...
| Main Authors: | , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2013
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/98079 http://hdl.handle.net/10220/13277 |
| _version_ | 1811682617572982784 |
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| author | 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. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences 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. |
| author_sort | Fric, Jan |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:59:41Z |
| format | Journal Article |
| id | ntu-10356/98079 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:59:41Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | ntu-10356/980792022-02-16T16:27:54Z Calcineurin/NFAT signalling inhibits myeloid haematopoiesis 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. School of Biological Sciences DRNTU::Science::Biological sciences 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. 2013-08-29T08:33:24Z 2019-12-06T19:50:20Z 2013-08-29T08:33:24Z 2019-12-06T19:50:20Z 2012 2012 Journal Article 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. 1757-4676 https://hdl.handle.net/10356/98079 http://hdl.handle.net/10220/13277 10.1002/emmm.201100207 22311511 en EMBO molecular medicine |
| spellingShingle | DRNTU::Science::Biological sciences 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. Calcineurin/NFAT signalling inhibits myeloid haematopoiesis |
| title | Calcineurin/NFAT signalling inhibits myeloid haematopoiesis |
| title_full | Calcineurin/NFAT signalling inhibits myeloid haematopoiesis |
| title_fullStr | Calcineurin/NFAT signalling inhibits myeloid haematopoiesis |
| title_full_unstemmed | Calcineurin/NFAT signalling inhibits myeloid haematopoiesis |
| title_short | Calcineurin/NFAT signalling inhibits myeloid haematopoiesis |
| title_sort | calcineurin nfat signalling inhibits myeloid haematopoiesis |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/98079 http://hdl.handle.net/10220/13277 |
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