The Roles of Lysosomes in Inflammation and Autoimmune Diseases

Abstract

Lysosomes perform a range of functions, some of which, such as degradation, are common to all cell types. Others, such as secretion or lysosomal exocytosis, are more specialised and tend to involve fusion of this organelle with the cell surface to release its contents. This review describes lysosomal regulation of the inflammatory glucocorticoid signaling pathways, and summarizes the roles of lysosomes in negatively or positively modulating the production of inflammatory cytokines. We also review the characteristic changes in lysosomal hydrolases and membrane proteins in common autoimmune diseases. Finally, future directions in lysosome research are proposed, with it being suggested that the role of lysosomes will continue to be of growing interest in immunity research.

Lysosomes as a therapeutic target

“…Secretory lysosomes regulate the release of both pro inflammatory and anti inflammatory cytokines, in a process that is depen dent on the type of stimulation. In addition, lysosomes degrade glucocorticoid receptors, which are essential to bind glucocorticoids, although the reasons are not known 78 . In this complex system, lysosomes execute anti inflammatory action via the phospholipase A2 and cyclooxygenase2 pathways, and also induce inflam mation through the IL1β-caspase1 pathway.…”

“…In both conditions (pro inflammatory and anti inflammatory), lysosomes act as indirect precursors for autoimmunity. However, induction and suppression of inflammatory signals are stimulus dependent 78 . Lysosomal cathepsins have a central role in degrading biological macromolecules in the lysosomes and in the immune response.…”

Microbial Diseases of Bivalve Mollusks: Infections, Immunology and Antimicrobial Defense

“…Humoral defense factors: The hemocyte degranulation and the extracellular release of lysosomal enzymes represent the first humoral defense mechanism that was investigated in marine bivalve mollusks [155], a strategy commonly described as a response to pathogens [156]. However, marine bivalve mollusks possess more selective extracellular tools to contrast invaders, including recognition and effector proteins, such as lectins, complement-like molecules, lipopolysaccharide- (LBP) and β-1,3-glucan-binding proteins (β-GBP), fibrinogen-related proteins (FREPs) and antimicrobial peptides (AMPs) [156,157,158].…”

A parasitic helminth-derived peptide that targets the macrophage lysosome is a novel therapeutic option for autoimmune disease

“…Alterations to any of these factors greatly affect immune cell function, and thus the ultimate immune response generated. As a consequence, these endosomal/lysosomal regulatory factors are being targeted for the development of anti-inflammatory drugs to treat pro-inflammatory and autoimmune disease (Kobayashi et al, 2013;Ge et al, 2014). This review focuses on the role of the lysosomal mediated activities of macrophages in the development of the proinflammatory immune responses that cause autoimmune disease, and the potential of helminth defence molecules (HDMs) to prevent these pro-inflammatory responses.…”