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Autophagy in autoimmune disease

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Abstract

Autophagy is a protective and life-sustaining process in which cytoplasmic components are packaged into double-membrane vesicles and targeted to lysosomes for degradation. This process of cellular self-digestion is an essential stress response and is cytoprotective by removing damaged organelles and proteins that threaten the cell’s survival. Key outcomes include energy generation and recycling of metabolic precursors. In the immune system, autophagy regulates processes such as antigen uptake and presentation, removal of pathogens, survival of short- and long-lived immune cells, and cytokine-dependent inflammation. In all cases, a window of optimal autophagic activity appears critical to balance catabolic, reparative, and inflammation-inducing processes. Dysregulation of autophagosome formation and autophagic flux can have deleterious consequences, ranging from a failure to “clean house” to the induction of autophagy-induced cell death. Abnormalities in the autophagic pathway have been implicated in numerous autoimmune diseases. Genome-wide association studies have linked polymorphisms in autophagy-related genes with predisposition for tissue-destructive inflammatory disease, specifically in inflammatory bowel disease and systemic lupus erythematosus. Although the precise mechanisms by which dysfunctional autophagy renders the host susceptible to continuous inflammation remain unclear, autophagy’s role in regulating the long-term survival of adaptive immune cells has recently surfaced as a defect in multiple sclerosis and rheumatoid arthritis. Efforts are underway to identify autophagy-inducing and autophagy-suppressing pharmacologic interventions that can be added to immunosuppressive therapy to improve outcomes of patients with autoimmune disease.

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Acknowledgments

This work was supported by the National Institutes of Health (R01 AR042547, R01 AI044142, HL 117913, R01 AI108906, and P01 HL058000 to CMW and R01 AI108891, R01 AG045779, and I01 BX001669 to JJG). ZY received fellowship support from the Govenar Discovery Fund.

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The authors declare that they have no competing interests.

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  1. Department of Medicine, Stanford University School of Medicine, CCSR Building Rm 2225, 269 Campus Drive West, Stanford, CA, 94305-5166, USA

    Zhen Yang, Jörg J. Goronzy & Cornelia M. Weyand

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  1. Zhen Yang
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  2. Jörg J. Goronzy
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  3. Cornelia M. Weyand
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Correspondence to Cornelia M. Weyand.

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Yang, Z., Goronzy, J.J. & Weyand, C.M. Autophagy in autoimmune disease. J Mol Med 93, 707–717 (2015). https://doi.org/10.1007/s00109-015-1297-8

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