Caspase-8 protein cuts a brake on immune defences

Brodsky, Igor E.

doi:10.1038/d41586-020-02994-y

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26 October 2020

Caspase-8 protein cuts a brake on immune defences

The enzyme caspase-8 can induce cell death or promote survival and the expression of inflammatory proteins. The discovery of a previously unknown caspase-8 target solves one mystery about immune-defence regulation.

Igor E. Brodsky⁰

Igor E. Brodsky
1. Igor E. Brodsky is in the Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine and Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
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Activation of the protein caspase-8 can have consequences that include triggering a type of cell death called apoptosis, preventing another type of cell death termed necroptosis, and promoting gene expression that leads to inflammation. How the activity of this single protein regulates these distinct functions is unclear. Writing in Nature, Gitlin et al.¹ shed light on how caspase-8 drives pro-inflammatory responses in mammalian cells (Fig. 1).

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Nature 587, 201-203 (2020)

doi: https://doi.org/10.1038/d41586-020-02994-y

References

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[1] Gitlin, A. D. et al. Nature 587, 275–280 (2020).
Article PubMed Google Scholar

[2] Tummers, B. & Green, D. R. Immunol. Rev. 277, 76–89 (2017).
Article PubMed Google Scholar

[3] van der Poll, T., van de Veerdonk, F. L., Scicluna, B. P. & Netea, M. G. Nature Rev. Immunol. 17, 407–420 (2017).
Article PubMed Google Scholar

[4] Chen, C., Edelstein, L. C. & Gelinas, C. Mol. Cell Biol. 20, 2687–2695 (2000).
Article PubMed Google Scholar

[5] Micheau, O., Lens, S., Gaide, O., Alevizopoulos, K. & Tschopp, J. Mol. Cell Biol. 21, 5299–5305 (2001).
Article PubMed Google Scholar

[6] Peterson, L. W. et al. J. Exp. Med. 214, 3171–3182 (2017).
Article PubMed Google Scholar

[7] Philip, N. H. et al. Proc. Natl Acad. Sci. USA 111, 7385–7390 (2014).
Article PubMed Google Scholar

[8] Weng, D. et al. Proc. Natl Acad. Sci. USA 111, 7391–7396 (2014).
Article PubMed Google Scholar

[9] Bidere, N., Su, H. C. & Lenardo, M. J. Annu. Rev. Immunol. 24, 321–352 (2006).
Article PubMed Google Scholar

[10] Chun, H. J. et al. Nature 419, 395–399 (2002).
Article PubMed Google Scholar

[11] Su, H. et al. Science 307, 1465–1468 (2005).
Article PubMed Google Scholar

[12] Kaiser, W. J. et al. Nature 471, 368–372 (2011).
Article PubMed Google Scholar

[13] Oberst, A. et al. Nature 471, 363–367 (2011).
Article PubMed Google Scholar

[14] Ch’en, I. L., Tsau, J. S., Molkentin, J. D., Komatsu, M. & Hedrick, S. M. J. Exp. Med. 208, 633–641 (2011).
Article PubMed Google Scholar

[15] Allam, R. et al. EMBO Rep. 15, 982–990 (2014).
Article PubMed Google Scholar

[16] Philip, N. H. et al. PLoS Pathog. 12, e1005910 (2016).
Article PubMed Google Scholar

[17] DeLaney, A. A. et al. Proc. Natl Acad. Sci. USA 116, 11926–11935 (2019).
Article PubMed Google Scholar

[18] Oberst, A. et al. Proc. Natl Acad. Sci. USA 104, 11280–11285 (2007).
Article PubMed Google Scholar

[19] Yamasoba, D. et al. Nature Microbiol. 4, 1532–1544 (2019).
Article PubMed Google Scholar

[20] Kaiser, W. J. & Offermann, M. K. J. Immunol. 174, 4942–4952 (2005).
Article PubMed Google Scholar

Caspase-8 protein cuts a brake on immune defences

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