Clinical and mechanistic studies of AIRE in rheumatoid arthritis
In rheumatoid arthritis (RA), activated pathogenic stromal cells, so-called fibroblast-like synoviocytes (FLS), in the joint act in concert with immune cells to drive chronic inflammation and destruction of tissue. About one hundred risk genes have been associated with RA and a quarter of these are upregulated in pathogenic FLS. We have shown that the transcription factor AIRE is one such gene and that it is expressed in the joint during the disease and promotes expression of interferon-regulated genes. AIRE plays an important role in the maturation of the immune system in the thymus where it counteracts autoimmunity. Its significance outside the thymus and especially in connective tissue cells in inflammation is largely unknown. A few studies, including ours, suggest that AIRE could be pro-inflammatory in the periphery.