Sjögren disease is characterized by chronic inflammation and autoantibody production against intracellular antigens such as TRIM21 (also known as Ro52); however, how TRIM21 becomes an autoantigen has remained unclear. Findings now demonstrate that lytic inflammatory cell death releases TRIM21, promoting the formation of immune complexes that are taken up by macrophages and contribute to loss of immune tolerance and inflammation.

Using mouse bone marrow-derived macrophages and HeLa cells, the researchers found that TRIM21 expression is upregulated by interferons and pathogen-associated inflammatory stimuli, and that TRIM21 is released during lytic forms of cell death (such as pyroptosis and necroptosis), but not apoptosis.