How do cells optimize luminal environments of endosomes/lysosomes for efficient inflammatory responses?

ABSTRACT

The endosome/lysosome compartments play pivotal roles in immune cell functions as signalling platforms. These intracellular compartments can efficiently restrict the localization of signalling complexes and temporally regulate signalling events to produce qualitatively different outcomes. Immune cells also exploit the endosome/lysosome system for signal transduction and intercellular communication to elicit immune responses. Antigen-presenting cells such as dendritic cells and macrophages take up pathogens by endocytosis and prepare antigens via the endosome/lysosome system. At the same time, pathogen-derived DNA and RNA are recognized by immune sensors at the endosome/lysosome compartments, which transmit signals to induce immune responses. Recent studies revealed the importance of controlling the endosomal/lysosomal environment for eliciting efficient signalling events at the endosomes/lysosomes. Many factors including pH, membrane potential, amino acid concentrations and lipid composition are finely tuned at the endosome/lysosome compartments, and dysregulation of these factors greatly affect immune cell functions. Redox-related molecules and various types of transporters are involved in the control of endosomal/lysosomal environment and could be good therapeutic targets for treating autoimmune diseases.