Tumor-necrosis factor -rich environment alters type-I interferon response to viral stimuli in patients with juvenile idiopathic arthritis by altering myeloid dendritic cell phenotype

The balance between the tumor-necrosis factor alpha (TNF alpha) and type-I interferon (T1IFN) pathways is crucial for proper immune function. Dysregulation of either pathway can contribute to autoimmune diseases development. Even though TNF alpha blockade has shown promising results in various autoimmune diseases, the effect on the balance between TNF alpha and T1IFN is elusive. We used targeted anti-TNF alpha therapies in juvenile idiopathic arthritis (JIA) as an experimental approach to study the cross-regulation between TNF alpha and type-I IFN. We found that TNF alpha-rich environment affected viral defense through the attenuation of T1IFN responses and affected the phenotype and distribution of myeloid dendritic cells, which are engaged in early viral infections. Anti-TNF alpha therapy normalized the observed deviations in JIA patients. We hypothesize that the inadequate immune response caused by a high TNF alpha environment could be projected to more frequent or lengthy viral infections and possibly play a role in the process of JIA disease development.