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Mast cell homeostasis and the JAK–STAT pathway

Genes & Immunity volume 11, pages 599–608 (2010)Cite this article

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Abstract

The Janus kinase/signal transducer and activator of transcription (JAK–STAT) pathway mediates important responses in immune cells. Activation of any of the four JAK family members leads to phosphorylation of one or more of seven STAT family members. Phosphorylation of STAT family members leads to their dimerization and translocation into the nucleus, in which they bind specific DNA sequences to activate gene transcription. Regulation of JAKs and STATs therefore has a significant effect on signal transduction and subsequent cellular responses. Mast cells are important mediators of allergic disease and asthma. These cells have the ability to cause profound inflammation and vasodilation upon the release of preformed mediators, as well as subsequent synthesis of new inflammatory mediators. The regulation of mast cells is therefore of intense interest for the treatment of allergic disease. An important regulator of mast cells, STAT5, is activated downstream of the receptors for immunoglobulin E, interleukin-3 and stem cell factor. STAT5 contributes to mast cell homeostasis, by mediating proliferation, survival, and mediator release. Regulators of the JAK–STAT pathway, such as the suppressors of cytokine signaling (SOCS) and protein inhibitor of activated STAT (PIAS) proteins, are required to fine tune the immune response and maintain homeostasis. A better understanding of the role and regulation of JAKs and STATs in mast cells is vital for the development of new therapeutics.

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Acknowledgements

This study was supported by grants from the National Institutes of Health (1R01AI59638 and U19AI077435).

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  1. Department of Biology and the VCU Allergy and Allergic Disease Cooperative Research Center, Virginia Commonwealth University, Richmond, VA, USA

    J K Morales, Y T Falanga, A Depcrynski, J Fernando & J J Ryan

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  1. J K Morales
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  2. Y T Falanga
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Morales, J., Falanga, Y., Depcrynski, A. et al. Mast cell homeostasis and the JAK–STAT pathway. Genes Immun 11, 599–608 (2010). https://doi.org/10.1038/gene.2010.35

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