Abstract
Autophagy, a constitutive intracellular degradation pathway, displays essential role in the homeostasis of immune cells, antigen processing and presentation, and many other immune processes. Perturbation of autophagy has been shown to be related to several autoimmune syndromes, including systemic lupus erythematosus. Therefore, modulating autophagy processes appears most promising for therapy of such autoimmune diseases. Autophagy can be said non-selective or selective; it is classified into three main forms, namely macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA), the former process being by far the most intensively investigated. The role of CMA remains largely underappreciated in autoimmune diseases, even though CMA has been claimed to play pivotal functions into major histocompatibility complex class II-mediated antigen processing and presentation. Therefore, hereby, we give a special focus on CMA as a therapeutic target in autoimmune diseases, based in particular on our most recent experimental results where a phosphopeptide modulates lupus disease by interacting with CMA regulators. We propose that specifically targeting lysosomes and lysosomal pathways, which are central in autophagy processes and seem to be altered in certain autoimmune diseases such as lupus, could be an innovative approach of efficient and personalized treatment.
Highlights
Autophagy, an intracellular degradation pathway in which lysosomes play a central role, has been raised as a hot topic in almost every aspect of cellular processes, including immune responses and regulation
The third main type of autophagy, chaperone-mediated autophagy (CMA) (Figure 1), is a process where client proteins containing specific motifs related to KFERQ [27] are selectively recognized by the cytosolic chaperone protein HSPA8/HSC70 present in a co-chaperones-rich complex that delivers them to the lysosome membrane
Manipulating MHCII antigen presentation of antigenic fragments acquired via the endo-lysosomal pathway certainly represents an efficient strategy to immunomodulate and selectively deviate the autoimmune response
Summary
An intracellular degradation pathway in which lysosomes play a central role, has been raised as a hot topic in almost every aspect of cellular processes, including immune responses and regulation. As it could be expected, any alteration of autophagy processes can potentially affect the normal course of cell metabolism and give rise to more or less dramatic cell malfunctioning. It is precisely what is more and more often emerging from experimental studies. Some autophagy failures have been suggested or experimentally demonstrated in situation of chronic inflammation and autoimmune diseases
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