Type III Interferons (Lambda Interferons) in Rheumatic Autoimmune Diseases

The last 2 decades have witnessed the discovery and characterization of a new family of cytokines with immunological characteristics similar to those described for type I interferons, type III or lambda interferons. Unraveling the molecular mechanisms underlying each type of interferon has allowed us to understand how some autoimmune diseases can be considered as interferonopathies. Under normal conditions, type III interferons play a key role in the defense against viruses by modulating the functioning of several types of innate and adaptive immune cells. These effects include upregulation of major histocompatibility complex molecules by myeloid dendritic cells, increased functioning of pattern recognition receptors by plasmacytoid dendritic cells, decreased activity of regulatory T cells, enhanced production of antibodies by plasmatic cells and increased expression of chemokines and adhesion molecules by leukocytes and endothelial cells. Notably, all these mechanisms have been described to boost autoimmunity, and type III interferons pathway activation has been related to the pathogenesis of autoimmune conditions such as systemic lupus erythematosus, systemic sclerosis and Sjögren's syndrome. This review provides an overview of the current evidence on the contribution of type III interferons in the pathogenesis of rheumatic autoimmune diseases in humans.