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Apoptosis

All's well that ends dead

Nature volume 400, pages 410–411 (1999)Cite this article

Too much of a good thing can be bad. Although expanded populations of lymphoid cells are a crucial defence against infectious agents, the immune system must then eliminate the excess cells after the pathogen has been destroyed. This depends on a cell-suicide process called apoptosis, and failure to destroy the surplus lymphoid cells leads the immune system to react against its own tissues (autoimmune effects)1. Reporting in Cell, Wang and colleagues2 describe a hitherto unknown type of autoimmune lymphoproliferative syndrome (ALPS) that arises from congenital mutations in caspase-10, a death protease that needs to be activated for apoptosis in mammals. The discovery not only expands our understanding of the genetic alterations that underlie ALPS, but also provides the first example of caspase mutations in human disease.

Caspases are the central executioners of mammalian apoptosis. They are produced in an enzymatically inactive form, and are activated in response to apoptotic stimuli. Active caspases degrade cellular components, resulting in eventual cell death3. Given that apoptosis is critical in maintaining proper cell physiology, disruption of the apoptotic machinery is thought to contribute to various diseases, ranging from neurodegenerative disorders to tumorigenesis4. So, it has long been suspected that mutations in caspases might be associated with certain inherited human conditions.

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Figure 1: Defective Fas signalling pathways underlie autoimmune lymphoproliferative syndrome (ALPS).

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Authors and Affiliations

  1. Biogen Inc., 14 Cambridge Center, Cambridge, 02142, Massachusetts, USA

    Timothy S. Zheng

  2. Section of Immmunobiology, Yale University School of Medicine, and the Howard Hughes Medical Institute, 310 Cedar Street, New Haven, 06510, Connecticut, USA

    Richard A. Flavell

Authors
  1. Timothy S. Zheng
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  2. Richard A. Flavell
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Zheng, T., Flavell, R. All's well that ends dead. Nature 400, 410–411 (1999). https://doi.org/10.1038/22659

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