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. Brodsky ⁰

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).
PubMed Article Google Scholar

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Caspase-8 protein cuts a brake on immune defences

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