Insights into Autophagic Machinery and Lysosomal Function in Cells Involved in the Psoriatic Immune-Mediated Inflammatory Cascade.

Abstract

Impaired autophagy, due to the dysfunction of lysosomal organelles, contributes to maladaptive responses by pathways central to the immune system. Deciphering the immune-inflammatory ecosystem is essential, but remains a major challenge in terms of understanding the mechanisms responsible for autoimmune diseases. Accumulating evidence implicates a role that is played by a dysfunctional autophagy-lysosomal pathway (ALP) and an immune niche in psoriasis (Ps), one of the most common chronic skin diseases, characterized by the co-existence of autoimmune and autoinflammatory responses. The dysregulated autophagy associated with the defective lysosomal system is only one aspect of Ps pathogenesis. It probably cannot fully explain the pathomechanism involved in Ps, but it is likely important and should be seriously considered in Ps research. This review provides a recent update on discoveries in the field. Also, it sheds light on how the dysregulation of intracellular pathways, coming from modulated autophagy and endolysosomal trafficking, characteristic of key players of the disease, i.e., skin-resident cells, as well as circulating immune cells, may be responsible for immune impairment and the development of Ps.