Articles in 2018

Environmental changes can sometimes be too rapid for genetic adaptation and result in a mismatch between our genetics and the environment. Osteoarthritis should be considered a mismatch disease owing to a rapid increase in prevalence that is associated with the modern lifestyle, diet and patterns of physical activity.

The deposition of calcium-containing crystals can result in various acute and chronic arthropathies. Understanding the biological effects of these crystals and underlying pathogenic mechanisms might inform on the development of future therapeutic strategies for these conditions.

Tight regulation of signalling cascades is vital for the correct development and function of bones and joints. A new study suggests that Notch signalling might join the likes of the transforming growth factor superfamily and Wnt signalling cascades as having an important function in joint homeostasis and disease.

Using mice with targeted deletion of the glucocorticoid receptor, a new study has examined the cell types that mediate the anti-arthritic effects of therapeutic glucocorticoids. Surprisingly, in the serum transfer-induced arthritis model, glucocorticoids target stromal cells rather than immune cells.

Inappropriate activation of Toll-like receptor 4 (TLR4) on resident fibroblasts, through the binding of damage-associated molecular patterns, is a potential driver of fibrosis in systemic sclerosis. New evidence suggests that targeting fibroblast-specific TLR4 or an accessory molecule MD2 could have therapeutic value.

Cancer immunotherapies that function as checkpoint inhibitors are an exciting development but are associated with immune-related adverse events that can occur in almost any organ. Among these events are complications that mirror established rheumatic diseases, so oncologists and rheumatologists must work together.

The two major lung complications in systemic sclerosis, lung fibrosis and pulmonary arterial hypertension, share some pathogenic mechanisms. Strategies for managing patients with these complications have greatly advanced in the past decade, and many tools and treatments are now available.

Preclinical rheumatoid arthritis (RA) is characterized by the presence of RA-related autoantibodies in the serum in the absence of clinical symptoms. This Review discusses the relationships during this period between mucosal alterations and the initiation of local and systemic anti-citrullinated protein antibody production.

Stimulator of interferon genes (STING), an important component of the cytosolic DNA sensing pathway, is an attractive therapeutic target for ameliorating interferon-driven systemic inflammation. New findings are shedding light on how STING functions and on a strategy to target STING therapeutically.