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The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity

Nature Immunology volume 1, pages 469–474 (2000)Cite this article

Abstract

Originally identified as a cell surface receptor that triggered the death of lymphocytes and tumor cells, it is now recognized that Fas (also known as CD95 or Apo-1) has distinct functions in the life and death of different cell types in the immune system. Fas signaling may also be involved in T cell costimulation and proliferation. Although Fas deficiency in humans and mice predisposes them towards systemic autoimmunity, Fas-FasL interactions can also facilitate organ-specific immunopathology. Proximal signaling by Fas and related receptors depends on subunit preassembly, which accounts for the dominant-negative effect of pathogenic receptor mutants and natural splice variants.

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Figure 1: Fas-FasL interactions mediate immune cell homeostasis.
Figure 2: Models for transmembrane signaling by Fas and related TNFR superfamily members.
Figure 3: Dominant interference in ALPS depends on the NH2-terminal PLAD.

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Acknowledgements

We thank L. Matis and J. Tschopp for suggestions and discussion. F. K. –M. C. is a fellow of the Cancer Research Institute and H. J. C. is a Howard Hughes Medical Institute–NIH Research Scholar.

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  1. Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892-1892, MD, USA

    Richard M. Siegel, Francis Ka-Ming Chan, Hyung J. Chun & Michael J. Lenardo

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  2. Francis Ka-Ming Chan
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Correspondence to Michael J. Lenardo.

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Siegel, R., Ka-Ming Chan, F., Chun, H. et al. The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity. Nat Immunol 1, 469–474 (2000). https://doi.org/10.1038/82712

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