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Autophagy genes in immunity

Nature Immunology volume 10, pages 461–470 (2009)Cite this article

Abstract

In its classical form, autophagy is a pathway by which cytoplasmic constituents, including intracellular pathogens, are sequestered in a double-membrane–bound autophagosome and delivered to the lysosome for degradation. This pathway has been linked to diverse aspects of innate and adaptive immunity, including pathogen resistance, production of type I interferon, antigen presentation, tolerance and lymphocyte development, as well as the negative regulation of cytokine signaling and inflammation. Most of these links have emerged from studies in which genes encoding molecules involved in autophagy are inactivated in immune effector cells. However, it is not yet known whether all of the critical functions of such genes in immunity represent 'classical autophagy' or possible as-yet-undefined autophagolysosome-independent functions of these genes. This review summarizes phenotypes that result from the inactivation of autophagy genes in the immune system and discusses the pleiotropic functions of autophagy genes in immunity.

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Figure 1: The autophagy pathway and its regulation.
Figure 2: Immunological processes involving autophagy.
Figure 3: Immunological processes involving autophagy genes.
Figure 4: Possible mechanisms by which alterations in autophagy may be involved in the pathogenesis of human Crohn's disease.

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Acknowledgements

We thank A. Diehl for medical illustration. Supported by the US National Institutes of Health (R01 CA074730, R01 CA096511, R01 AI054483, R01 AI065982 and U54 AI057160 to H.W.V., and R01 AI151267 and R01 CA109618 to B.L.), the Howard Hughes Medical Institute (B.L.) and the Ellison Medical Foundation (B.L.).

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  1. Department of Pathology and Immunology, Department of Molecular Microbiology and Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA

    Herbert W Virgin

  2. Department of Internal Medicine and Department of Microbiology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Beth Levine

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Virgin, H., Levine, B. Autophagy genes in immunity. Nat Immunol 10, 461–470 (2009). https://doi.org/10.1038/ni.1726

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