Programmed necrosis and autophagy in immune function

Authors

  • Jennifer V. Lu,

    1. Institute for Immunology and Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA
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  • Craig M. Walsh

    Corresponding author
    • Institute for Immunology and Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, USA
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Correspondence to:

Craig M. Walsh

Institute for Immunology and Department of Molecular Biology and Biochemistry

University of California, Irvine

Irvine, CA 92697, USA

Tel.: +1 949 824 8487

Fax: +1 949 824 8551

e-mail: cwalsh@uci.edu

Summary

It has long been known that apoptosis is vital to the generation and maintenance of proper adaptive immune function. An example is the essential requirement for apoptotic signaling during the generation of self-tolerant lymphocytes: the apoptotic death of B and T cells with overt autoreactivity is essential to central tolerance. More recently, the contributions of additional processes including cellular autophagy and programmed necrosis have been implicated in controlling both innate and adaptive immune functions. Evidence has been provided to demonstrate that the death of cells following ligation of death receptors (DRs), a subfamily of cell surface molecules related to tumor necrosis factor receptor 1, is not exclusively the domain of caspase-dependent apoptosis. In cells lacking the capacity to activate caspase-8 following DR ligation, cell death instead occurs via programmed necrosis, or as it has been recently termed, ‘necroptosis’. This death process depends on RIP1 and RIP3, serine/threonine kinases that are recruited by DRs, and likely by other cellular signals including DNA damage and antigen receptor ligation. The generation of RIP1/RIP3 containing ‘necrosomes’ activates downstream necroptotic signaling that ultimately targets cellular energetic metabolism. Also related to cellular metabolic regulation, cellular autophagy has also been found to play unique and important roles in immunity. In this review, we describe the roles of necroptosis and autophagy in innate and adaptive immunity and speculate on the intriguing interplay between these two cellular processes.

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