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Type I interferon has a crucial role in the immunopathogenesis of systemic lupus erythematosus (SLE). Analysis of CD4+ T cells from individuals with SLE now shows that type I interferon intervenes with the transcriptional regulators AHR and JUN to downregulate expression of IL-22, which promotes tissue regeneration, and upregulate the expression of CXCL13, which supports lymphoid structure formation.
This Review provides an update on developments in Janus kinase inhibitors, including new disease indications and adverse effects. The authors discuss issues surrounding selectivity and efficacy, as well as new routes for administration of Janus kinase inhibitors.
Holers and colleagues review current data linking immune mechanisms and dysbiosis at distinct mucosal sites to risk of rheumatoid arthritis (RA). Their newly introduced causal mucosal endotypes hypothesis suggests that lung-, gut-, or oral-associated endotypes might drive the pathogenesis and progression of RA, and highlights associated research directions towards preventive and therapeutic strategies in RA.
Emerging data suggest that resident cells and locally produced mediators interact with nerves in the joint to promote pain in rheumatoid arthritis. This Review discusses the potential neuro–immune–stromal interactions promoting joint pain and highlights the need for an interdisciplinary approach to therapeutic development.
Researchers have identified a mechanistic link between SARS-CoV-2 infection and multisystem inflammatory syndrome in children, providing evidence for the involvement of molecular mimicry.
The first guidelines for the screening, monitoring and treatment of interstitial lung disease (ILD) in patients with systemic autoimmune rheumatic diseases (SARDs) are now available after a major multidisciplinary effort by the ACR and the American College of Chest Physicians. These guidelines demonstrate that multidisciplinary collaborations can improve SARD-ILD management.
This Review explores the genetic basis of systemic lupus erythematosus, including the role of enhancers in the MHC region, the 3D structure of DNA and various pathway-specific mechanisms. These findings enhance disease understanding and inform improved diagnosis and treatment strategies.
Autoimmune diseases such as systemic lupus erythematosus preferentially affect women, and multiple hypotheses are under investigation to elucidate this phenomenon. Emerging research suggests that multiple pathophysiological mechanisms and pathways are likely involved, including several that involve the X chromosome, but is skewing of X chromosome inactivation one of them?
Immune health has been considered impossible to assess through the use of traditional biomarkers. The newly devised immune health metric (IHM) integrates diverse biological data to quantify immune function, offering a comprehensive indicator for the evaluation of immune health. The potential of the IHM to distinguish healthy individuals from patients with monogenic or polygenic immune-mediated diseases might lead to revolutionary changes in treatment strategies for rheumatic diseases.
Cardiovascular involvement is one of the many manifestations of rheumatic immune-mediated inflammatory diseases (IMIDs) that increase mortality. The pathogenesis of atherosclerosis and inflammatory cardiomyopathies involves inflammatory pathways common with those operating and targeted in rheumatic IMIDs. Here, Maya Buch and colleagues discuss implications of these shared pathways for the prevention, detection and management of cardiovascular involvement in patients with rheumatic IMIDs, while highlighting complexities and open questions.
In a new study, researchers use M2 macrophage exosomes and membranes to disguise a tri-drug-carrying nanosystem that reduces inflammation and urate levels in rats with gouty arthritis.
Increasing diversity in genomic studies is essential to advance precision medicine and health equity in rheumatic diseases. Addressing structural and logistical barriers to include underrepresented populations, particularly in Africa and Latin America, could improve our understanding of rheumatic diseases and lead to better healthcare outcomes for all.
The PDZ domain-containing scaffold protein PDZK1 is downregulated in osteoarthritic chondrocytes and is linked to mitochondrial dysfunction and chondrocyte senescence.
Ion channels have key functions in chondrocytes, bone cells, immune cells and neurons. Liu and colleagues discuss how these functions might contribute to cartilage degeneration, bone formation inflammation and pain in osteoarthritis, and highlight the therapeutic potential of ion channel modulators.
Paediatric rheumatology has seen many notable developments in the past 25 years, including the introduction of the concept of autoinflammation and a greater understanding of the genetics and pathogenesis of inflammatory diseases. In this Perspective, Ozen and Aksentijevich discuss how these and other discoveries have transformed the field and herald improvements in patient care.
In this Review, the authors explore the complex interactions between osteoarthritis-related pain and obesity, adipose tissue dysfunction and metabolic syndrome, and discuss how knowledge of these relationships could help improve pain management and identify new therapeutic options.
CAR T cell therapy shows promise for achieving long-term drug-free remission in various autoimmune diseases. This Review discusses the ongoing challenges and unanswered questions of CAR T cell therapy in autoimmune diseases, including pre-procedural, procedural and post-procedural considerations.
Glucocorticoids are important anti-inflammatory and immunosuppressive drugs and potent regulators of metabolism. However, their immune and metabolic effects have been treated as separate entities. New research is shedding light onto the intersection between the immunoregulatory and metabolic effects of glucocorticoids.
