Autophagy and systemic autoimmune diseases

Autophagy (or macroautophagy) is an evolutionarily conserved lysosomal degradation pathway in eukaryotic organisms. During autophagy, portions of the cytoplasm and intracellular organelles are sequestered within characteristic double-membrane vesicles known as autophagic vacuoles or autophagosomes and are finally delivered to lysosomes for bulk degradation (1). Autophagy is involved in many physiological processes including immune system development and maturation. Autophagy has emerged indeed as a key mechanism in orchestrating innate and adaptive immune responses to intracellular pathogens and it contributes to MHC class II-mediated presentation of intracellular antigens to CD4+ T lymphocytes (2). Recently, aberrant regulation of autophagy has been linked to several autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) (3). Autophagy in innate and adaptive immunity Autophagy contributes to innate immunity by protecting the cytosol from colonization by intracellular microbial pathogens and is constitutively activated in antigen-presenting cells (APCs), such as DCs, macrophages, and B cells taking part in antigen presentation (4). Extracellular antigens captured by APCs are delivered to autophagosomes, which utilize hydrolases from endosomes (such as cathepsins) to generate immunogenic peptides and load them onto MHC class II molecules for presentation to CD4+ T cells (5). Autophagy-dependent antigen presentation has a crucial role also in the maintenance of immunological tolerance (6). B and T lymphocytes are key players in autoimmune disease pathogenesis and they seem to be particularly dependent on autophagy for their development, survival and proliferation (7).