Figure 1.

Proposed Role of TRIM in Chronic Inflammatory Diseases

Sterile inflammation is a hallmark of autoimmune diseases, autoinflammatory diseases, and inflammatory diseases such as atherosclerosis. Several danger-associated molecular patterns (DAMPs) have been shown to induce inflammation in innate immune cells. Metabolic intermediates including oxidized low-density lipoprotein (ox-LDL) and mevalonate induce epigenetic modifications and metabolic rewiring in monocytes and macrophages, resulting in a hyperinflammatory, hypermetabolic state. These are produced in high levels in atherosclerosis and hyper-IgD syndrome, respectively, and therefore TRIM may play an integral role in the chronic inflammation seen in these diseases. Other DAMPs have been proposed as inducers of TRIM in autoimmunity, including citrullinated histones in RA, and monosodium urate in SLE patients with cardiovascular comorbidities. The epigenetic reprogramming in TRIM results in an increased production of pro-inflammatory cytokines, which is also consistently reflected in the serum levels of patients with autoimmune and autoinflammatory diseases.