The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency
Abstract
Apoptosis is a form of programmed cell death that is controlled by aspartate-specific cysteine proteases called caspases. In the immune system, apoptosis counters the proliferation of lymphocytes to achieve a homeostatic balance, which allows potent responses to pathogens but avoids autoimmunity. The CD95 (Fas, Apo-1) receptor triggers lymphocyte apoptosis by recruiting Fas-associated death domain (FADD), caspase-8 and caspase-10 proteins into a death-inducing signalling complex. Heterozygous mutations in CD95, CD95 ligand or caspase-10 underlie most cases of autoimmune lymphoproliferative syndrome (ALPS), a human disorder that is characterized by defective lymphocyte apoptosis, lymphadenopathy, splenomegaly and autoimmunity. Mutations in caspase-8 have not been described in ALPS, and homozygous caspase-8 deficiency causes embryonic lethality in mice. Here we describe a human kindred with an inherited genetic deficiency of caspase-8. Homozygous individuals manifest defective lymphocyte apoptosis and homeostasis but, unlike individuals affected with ALPS, also have defects in their activation of T lymphocytes, B lymphocytes and natural killer cells, which leads to immunodeficiency. Thus, caspase-8 deficiency in humans is compatible with normal development and shows that caspase-8 has a postnatal role in immune activation of naive lymphocytes.
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Cites
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Cited by
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Necroptosis: The Release of Damage-Associated Molecular Patterns and Its Physiological Relevance
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Metadata
- Authors
- Chun, H. J., Zheng, L., Ahmad, M., Wang, J., Speirs, C. K., Siegel, R. M., Dale, J. K., Puck, J., Davis, J., Hall, C. G., Skoda-Smith, S., Atkinson, T. P., Straus, S. E., & Lenardo, M. J.
- Venue
- Nature
- Published
- 2002-09
- Volume
- 419
- Issue
- 6905
- Pages
- 395-399
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2089244519
- Cited by
- 708
- References
- 25
- FWCI
- 16.61
- Type
- journal article
- Language
- en
- Open access
- closed
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- Chun, H. J., Zheng, L., Ahmad, M., Wang, J., Speirs, C. K., Siegel, R. M., Dale, J. K., Puck, J., Davis, J., Hall, C. G., Skoda-Smith, S., Atkinson, T. P., Straus, S. E., & Lenardo, M. J. (2002). Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature. https://doi.org/10.1038/nature01063
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