Etiology and Immunopathogenesis of Sarcoidosis: Novel Insights

Sarcoidosis is a disorder of unknown etiology. It is a systemic disease, frequently involving the lungs, skin, eyes, and lymph nodes. It is characterized by formation of noncaseating granulomas at the site(s) of disease. Sarcoidosis has a complex disease pathogenesis, with involvement of both the innate and adaptive immune systems. Several innate immune system receptors including NOD-like receptors and Toll-like receptors appear to be involved in the development of sarcoidosis as well as cellular players such as dendritic cells and macrophages. Furthermore, lymphocytes from the adaptive immune system including Th1, Th17, regulatory T cells, and B cells are likely to play a role in the sarcoidosis disease pathogenesis as well. Possibly, genetic susceptibility and exposure to particular etiologic agents including mycobacterial and propionibacterial antigens, metals, and silica can cause sarcoidosis. Besides exogenous triggers, also self-compounds such as serum amyloid A and vimentin, have been found to play a role in the development of sarcoidosis. It is likely that sarcoidosis does not have one single cause but rather is the result of the interplay between different etiologic agents and the immune system in predisposed individuals.