Selective role of calcineurin in haematopoiesis and lymphopoiesis

Elena M. Gallo, Lena Ho, Monte M. Winslow, Tracy L. Staton, Gerald R. Crabtree

Research output: Contribution to journalArticle

Abstract

The calcineurin/NFAT (nuclear factor of activated T-cells) signalling pathway is essential for many aspects of vertebrate development and is the target of the widely used immunosuppressive drugs FK506 and cyclosporine A. The basis for the therapeutic specificity of these drugs has remained unclear, as calcineurin is expressed ubiquitously. By inactivating calcineurin during haematopoietic development, we found that although this signalling pathway has an important, non-redundant role in the regulation of lymphocyte developmental checkpoints, it is not essential for the development of blood myeloid lineages. These studies have shown that the specificity of calcineurin inhibitors arises from the selective use of calcineurin at distinct developmental stages. The requirement for calcineurin/NFAT in the development of the adaptive but not of the innate immune system is consistent with the idea that the evolutionary appearance of this pathway was involved in the emergence of vertebrates.

Original languageEnglish (US)
Pages (from-to)1141-1148
Number of pages8
JournalEMBO Reports
Volume9
Issue number11
DOIs
StatePublished - Sep 29 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Gallo, E. M., Ho, L., Winslow, M. M., Staton, T. L., & Crabtree, G. R. (2008). Selective role of calcineurin in haematopoiesis and lymphopoiesis. EMBO Reports, 9(11), 1141-1148. https://doi.org/10.1038/embor.2008.174