Lymphocyte Autophagy in Homeostasis, Activation, and Inflammatory Diseases

Abstract

Autophagy is a catabolic mechanism, allowing the degradation of cytoplasmic content via lysosomal activity. Several forms of autophagy are described in mammals. Macroautophagy leads to integration of cytoplasmic portions into vesicles named autophagosomes that ultimately fuse with lysosomes. Chaperone-mediated autophagy is in contrast the direct translocation of protein in lysosomes. Macroautophagy is central to lymphocyte homeostasis. Although its role is controversial in lymphocyte development and in naive cell survival, it seems particularly involved in the maintenance of certain lymphocyte subtypes. Its importance in memory B and T cells biology has recently emerged. Moreover, some effector cells like plasma cells rely on autophagy for survival. Autophagy is central to glucose and lipid metabolism, and to the maintenance of organelles like mitochondria and endoplasmic reticulum. In addition macroautophagy, or individual components of its machinery, are also actors in antigen presentation by B cells, a crucial step to receive help from T cells, this crosstalk favoring their final differentiation into memory or plasma cells. Autophagy is deregulated in several autoimmune or autoinflammatory diseases like systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and Crohn’s disease. Some treatments used in these pathologies impact autophagic activity, even if the causal link between autophagy regulation and the efficiency of the treatments has not yet been clearly established. In this review, we will first discuss the mechanisms linking autophagy to lymphocyte subtype survival and the signaling pathways involved. Finally, potential impacts of autophagy modulation in lymphocytes on the course of these diseases will be approached.

Beyond Anti-viral Effects of Chloroquine/Hydroxychloroquine

“…Autophagosomes ultimately fuse with lysosomes leading to the degradation of their content. Autophagy is a major player in immunity ( 11 ). It contributes to reduce inflammation by modulating type I interferon production and inflammasome activity.…”

GABA potentiate the immunoregulatory effects of Lactobacillus brevis BGZLS10-17 via ATG5-dependent autophagy in vitro

“…cess of autophagy is commonly monitored by the expression analysis of different proteins associated with autophagosome initiation, nucleation, elongation and regulation 35 . The most indicative marker for autophagy is the conjugation of cytosolic form of microtubule-associated protein light chain 3, LC3 (LC3I), with a phosphatidylethanolamine (PE) that, when integrated into the autophagosomal membrane is named LC3II 36 . LC3II remains associated during the whole autophagy process, and the closed autophagic vesicle is then addressed to lysosomes during the maturation phase.…”

Podocytes and autophagy: a potential therapeutic target in lupus nephritis

“…The difference in the types of injuries and severity of injuries may produce different outcome of autophagy, in that a certain degree of autophagic activity can maintain tissue homeostasis, whereas excessive autophagic activity results in cell death, especially in chronic inflammation and aging circumstances. Furthermore, it also possible that in some populations, such as memory cells, macroautophagy contributes to survival and chronic activation; in others such as naive cells, or Treg cells [47], the continuous generation of autophagosomes is not balanced by their degradation and leads to cell death [48,49]. Future investigations, for instance by using cell-specific and targeted autophagic gene knockout mice, are necessary to elucidate and clarify the precise functional role of autophagy in lupus.…”