Autophagy and Rheumatoid Arthritis: Current Knowledges and Future Perspectives

Abstract

Autophagy is a degradation mechanism by which cells recycle cytoplasmic components to generate energy. By influencing lymphocyte development, survival, and proliferation, autophagy regulates the immune responses against self and non-self antigens. Deregulation of autophagic pathway has recently been implicated in the pathogenesis of several autoimmune diseases, including rheumatoid arthritis (RA). Indeed, autophagy seems to be involved in the generation of citrullinated peptides, and also in apoptosis resistance in RA. In this review, we summarize the current knowledge on the role of autophagy in RA and discuss the possibility of a clinical application of autophagy modulation in this disease.

Increased intestinal barrier permeability in patients with moderate to severe plaque‐type psoriasis

“…4 Therefore, innate immune reaction may induce ATG-related protein expression and autophagy in histiocytes and giant cells in the cutaneous granulomatous foci. Although autophagy is implicated in the pathogenesis of rheumatoid arthritis, 5 we could not detect enough ATG-related protein expression in rheumatoid nodules. This may be due to the disease severity, stage or duration, but further studies are required to clarify the reason.…”

“…4 Prevalence of HLA-B*27 is higher in psoriatic patients versus controls (20-35% vs 7.5%) and it may represent a risk factor for gut permeability. 5 In our study, linear correlation between zonulin and LPS levels may suggest a bacterial translocation from the intestinal lumen to the blood circulation due to intestinal barrier dysfunction. LPS, as it is known, can induce the activation of inflammatory cascade, linking the Toll-like receptor 4/myeloid differentiation factor 2 receptor complex.…”

Lysosomes as a therapeutic target

“…2). Although the mechanism of action of these agents is not fully elucidated, it is well established that CQ and HCQ display pleiotropic activity [208][209][210] and have impor tant deleterious properties. In certain settings, they have been claimed to operate by interacting directly with TLR ligands and not through an effect on the lysosomal pH, for example 211 .…”

Molecular and Cellular Pathways Contributing to Joint Damage in Rheumatoid Arthritis

“…In addition, autophagy of macrophages plays an essential role in the pathogenesis of RA [44], which can increase the number of osteoclasts contributing to enhanced bone resorption activity.…”