J Rheum Dis.  2016 Aug;23(4):202-211. 10.4078/jrd.2016.23.4.202.

Pathogenic Role of Autophagy in Rheumatic Diseases

• Choi YJ
• Yoo WH

• KMID: 2352464
• DOI: http://doi.org/10.4078/jrd.2016.23.4.202

Abstract

Autophagy is a principle catabolic process mediated by lysosomes in eukaryotic cells. This is an intracellular homeostatic mechanism crucial for degradation in acidic lysosomal compartments of waste components from the cytoplasm. Autophagy research was initially focused on its degradation mechanism, but focus is now shifting to its effects on immunity. It contributes to detection and removal of pathogens as well as regulation of inflammasomes and neutrophil extracellular traps. Moreover, it is pivotal in antigen presentation and immune cell maturation, survival and homeostasis. The importance of autophagic pathways in normal and dysregulated immunity has become increasingly recognized in the past several years. Dysregulation of the autophagic pathway is implicated in the pathogenesis of several rheumatic diseases. In this review, we summarize the immunological function of autophagy in innate and adaptive immunity, and the functions of autophagy in the pathogenesis of rheumatic diseases.

Keyword

Autophagy; Immunity; Rheumatic diseases; Systemic lupus erythematosus; Rheumatoid arthritis

MeSH Terms

Adaptive Immunity
Antigen Presentation
Arthritis, Rheumatoid
Autophagy*
Cytoplasm
Eukaryotic Cells
Extracellular Traps
Homeostasis
Inflammasomes
Lupus Erythematosus, Systemic
Lysosomes
Rheumatic Diseases*
Inflammasomes

Figure

• 

  Figure 1. Autophagic pathway. The autophagy pathway is induced by inactivation of mTOR complex. Starvation or energy ex-haustion inhibits mTOR complex, it enables ULK complex to be dissociated from mTOR complex. The stimulated ULK complex translocates to the ER, and activates class III PI3K complex. The PI3P, which is essential for autophagosomal membrane nucleation, is formed by activated class III PI3K complex. The phagophore expansion and closure mediated through conversion of LC3-I to LC3-II occurred with the help of ATG7-induced, ATG5-ATG12 complex mediated lipidation. After formation of autophagosome, it fuses with lysosome to form autolysosome and sequestered materials are degradaed by lysosomal hydrolase. Adapted from Figure 1 in the article of Levine et al. [20] (Nature 2011;469:323-35). mTOR: mammalian target of rapamycin, ULK: UNC-51-like kinase, ER: endoplasmic reticulum, PI3K: phosphatidylinositol 3-kinase, PI3P: phosphatidylinositol-3-phosphate, LC: light chain, ATG: au-tophagy-related protein, DEPTOR: DEP domain containing mTOR-interacting protein, FIP200: focal adhesion kinase family inter-acting protein of 200 kDA, Gβ L/mLST8: G protein β subunit-like protein, PRAS40: protein-rich AKT substrate 40 kDA, RAPTOR: regulatory associated protein of mTOR, PIK3C3: PI3K catalytic subunit type 3, PIK3R4: PI3K regulatory subunit 4, UVRAG: UV radiation resistance associated gene protein.

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