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Review
. 2023 Jul 2;4(4):e311.
doi: 10.1002/mco2.311. eCollection 2023 Aug.

Modulation of the immunity and inflammation by autophagy

Ting Gan  1   2   3   4 , Shu Qu  1   2   3   4 , Hong Zhang  1   2   3   4 , Xu-Jie Zhou  1   2   3   4
Affiliations
Review

Modulation of the immunity and inflammation by autophagy

Ting Gan et al. MedComm (2020). .

Abstract

Autophagy, a highly conserved cellular self-degradation pathway, has emerged with novel roles in the realms of immunity and inflammation. Genome-wide association studies have unveiled a correlation between genetic variations in autophagy-related genes and heightened susceptibility to autoimmune and inflammatory diseases. Subsequently, substantial progress has been made in unraveling the intricate involvement of autophagy in immunity and inflammation through functional studies. The autophagy pathway plays a crucial role in both innate and adaptive immunity, encompassing various key functions such as pathogen clearance, antigen processing and presentation, cytokine production, and lymphocyte differentiation and survival. Recent research has identified novel approaches in which the autophagy pathway and its associated proteins modulate the immune response, including noncanonical autophagy. This review provides an overview of the latest advancements in understanding the regulation of immunity and inflammation through autophagy. It summarizes the genetic associations between variants in autophagy-related genes and a range of autoimmune and inflammatory diseases, while also examining studies utilizing transgenic animal models to uncover the in vivo functions of autophagy. Furthermore, the review delves into the mechanisms by which autophagy dysregulation contributes to the development of three common autoimmune and inflammatory diseases and highlights the potential for autophagy-targeted therapies.

Keywords: autoimmune diseases; autophagy; immunity; inflammation; pathogenesis.

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Conflict of interest statement

All authors have approved of the manuscript and declare no potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The process and molecular mechanism of autophagy. †Autophagy proceeds through a series of sequential phases, including autophagy initiation, nucleation of the autophagosome, elongation and closure of the autophagosome, and fusion of the autophagosome with lysosome. The process is mediated by a set of proteins encoded by autophagy‐related (ATG) genes.
FIGURE 2
FIGURE 2
The roles of autophagy deficiency in pathogenesis of inflammatory bowel diseases (IBD). †Defective autophagy can affect gut microbiota composition, disrupt intestinal epithelial homeostasis, and amplify intestinal inflammation in IBD.
FIGURE 3
FIGURE 3
The roles of autophagy dysregulation in the pathogenesis of systemic lupus erythematosus (SLE)/lupus nephritis (LN). †A deficiency in autophagy or noncanonical autophagy can result in defective processing and degradation of dead cells, overproduction of inflammatory cytokines, and autoreactive B cell activation, leading to increased proliferation and differentiation of B cell. Plasmacytoid dendritic cells (pDCs) can trigger the production of type I interferon by internalizing immune complexes via noncanonical autophagy. In the context of LN, autophagy can protect podocytes from injury, such as pathogenic autoantibodies, and interferon‐α.
FIGURE 4
FIGURE 4
The roles of autophagy dysregulation in the pathogenesis of multiple sclerosis (MS). †Autophagy can act as a two‐edged sword in MS. While inhibiting autophagy may alleviate the inflammatory immune response by interfering with antigen presentation and specific T cell activation, it can also accelerate the accumulation of undesired substrates, such as apoptotic cells, myelin and axonal fragments, and protein aggregates.
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