Contribution of toll-like receptors and the NLRP3 inflammasome in rheumatoid arthritis pathophysiology

Rheumatoid arthritis (RA) is a progressive autoimmune disease that is characterized by inflammation of the synovial joints leading to cartilage and bone damage. The pathogenesis is sustained by the production of pro-inflammatory cytokines including tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6, which can be targeted therapeutically to alleviate disease severity. Several innate immune receptors are suggested to contribute to the chronic inflammation in RA, through the production of pro-inflammatory factors in response to endogenous danger signals. Much research has focused on toll-like receptors and more recently the nucleotide-binding domain and leucine-rich repeat pyrin containing protein-3 (NLRP3) inflammasome, which is required for the processing and release of IL-1β. This review summarizes the current understanding of the potential involvement of these receptors in the initiation and maintenance of inflammation and tissue damage in RA and experimental arthritis models

The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication.

The circadian clock regulates immune responses to microbes and affects pathogen replication, but the underlying molecular mechanisms are not well understood. Here we demonstrate that the circadian components BMAL1 and REV-ERBα influence several steps in the hepatitis C virus (HCV) life cycle, including particle entry into hepatocytes and RNA genome replication. Genetic knock out of Bmal1 and over-expression or activation of REV-ERB with synthetic agonists inhibits the replication of HCV and the related flaviruses dengue and Zika via perturbation of lipid signaling pathways. This study highlights a role for the circadian clock component REV-ERBα in regulating flavivirus replication

Defining renal phenotype in Alstr\uf6m syndrome

Alstr\uf6m syndrome (AS) is a rare autosomal recessive ciliopathy with a wide spectrum of clinical features, including cone-rod retinal dystrophy, neuronal deafness, severe insulin resistance and major organ failure. The characteristics of renal disease in the syndrome have not been systematically described. The aim of this study is to define the onset and progression of renal disease in AS