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Crosstalk with the Jak-STAT Pathway in Inflammation

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Jak-Stat Signaling : From Basics to Disease

Abstract

The Jak-STAT signaling pathway is activated by multiple immune cytokines and plays a key role in mediating inflammatory responses. The functional outcomes of Jak-STAT signaling are modulated by signaling crosstalk with heterologous signaling pathways. Conversely, Jak-STAT signaling regulates cell responses to multiple cytokines and inflammatory factors. Emerging evidence suggests that on balance Jak-STAT signaling is pathogenic in chronic inflammatory disorders, as Jak inhibitors have demonstrated efficacy in preclinical disease models and early clinical trials in rheumatoid arthritis (RA). This review describes Jak-STAT signaling crosstalk with pathways activated by inflammatory cytokines such as TNF-α, pattern recognition receptors such as Toll-like receptors, and ITAM-associated receptors, including crosstalk at the level of chromatin modification and gene expression. The Jak-STAT pathway is placed within the context of a signaling network that determines functional responses and outcomes during inflammation and in chronic inflammatory diseases such as RA.

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Acknowledgements

This work was supported by grants from the National Institutes of Health, USA.

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Authors and Affiliations

  1. Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA

    Lionel B. Ivashkiv

  2. Graduate Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA

    Lionel B. Ivashkiv

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Correspondence to Lionel B. Ivashkiv .

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  1. , Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 9/4, Vienna, 1030, Austria

    Thomas Decker

  2. , Animal Breeding and Genetics, University of Vienna, Veterinärplatz 1, Vienna, 1210, Austria

    Mathias Müller

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Ivashkiv, L.B. (2012). Crosstalk with the Jak-STAT Pathway in Inflammation. In: Decker, T., Müller, M. (eds) Jak-Stat Signaling : From Basics to Disease. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0891-8_19

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