Pathogenesis articles from across Nature Portfolio

Trace levels of circulating cytokines correlate with the prevalence of cardiovascular symptoms following COVID-19.

We generated a mouse model to investigate the mechanistic basis of inborn errors of immunity caused by heterozygous BCL11B mutation. The BCL11B mutant protein interfered with BCL11A function, impairing T cell and neuronal development. Mutant BCL11B also failed to antagonize TCF1 function, leading to aberrant natural killer cell differentiation in the thymus.

In a cohort of 50,556 South Asian individuals, partitioned polygenic scores helped identify genetic susceptibility to insulin deficiency and unfavorable fat distribution as key drivers of young-onset T2D diagnosis and faster progression to diabetes-related complications.

Trace levels of circulating cytokines correlate with the prevalence of cardiovascular symptoms following COVID-19.

We generated a mouse model to investigate the mechanistic basis of inborn errors of immunity caused by heterozygous BCL11B mutation. The BCL11B mutant protein interfered with BCL11A function, impairing T cell and neuronal development. Mutant BCL11B also failed to antagonize TCF1 function, leading to aberrant natural killer cell differentiation in the thymus.

Rheumatic symptoms such as joint inflammation and pain are known features of SARS-CoV-2 infection, though the mechanisms remain unclear. Au and colleagues identified the interaction between the viral spike protein and the endothelin-1 (ET-1) signaling pathway as a cause of osteochondral damage. Their study showed that macitentan, an FDA-approved ET-1 receptor antagonist, reduced joint damage and inflammation in a hamster model, suggesting ET-1 as a potential therapeutic target for viral-induced osteoarthritis (OA).

Farnesyl pyrophosphate (FPP), an intermediate of cholesterol biosynthesis in the mevalonate pathway, prolongs the survival of migratory dendritic cells (mig-DCs) by remodelling mitochondrial structure and metabolism. Treating a mouse model of systemic lupus erythematosus with simvastatin (an inhibitor of this pathway) led to recovery from dysregulation in mig-DCs and ameliorated systemic autoimmune pathogenesis.